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Vol. I, Issue I

July 2019Vol. III, Issue VII

S&A PHARMANEWSLETTER

E-337, East of KailashNew Delhi - 110065, INDIA

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BENGALURUUnit No. 101, 10th Floor Sakhar Bhavan, Plot No. 230Ramnath Goenka MargNariman Point, Mumbai - 400021, INDIA

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S i n g h a n d A s s o c i a t e s

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Manoj K. Singh Founding Partner

EDITORIAL

The drug regulatory authority of any country should be robust as it is responsible for taking all necessary regulatory action in research, manufacturing, and distri-bution to ensure the quality of drugs. It forms the backbone in running the health care system of the country. Therefore, time to time surveillance and monitoring of regulatory guidelines should be encouraged to prepare for the healthcare chal-lenges as and when they arrive.

We are pleased to present this Vol. III Issue VII of S&A – Pharma Newsletter. Through this newsletter, we aim to share recent information allied to regulatory reforms and updates from pharmaceutical sector in India as well as from foreign jurisdictions, based on information collated through research and appraisal of ap-plicable statutory provisions.

In the present issue, we start with an article on Central Government imposing a ban on the use of Colestin in livestock, which is a multisectoral approach to tackle Anti-Microbial Resistance. Going forward, the issue throws some light on the elev-enth amendment of the Drug and Cosmetics Act, 2019, related to permanency and renewal of the drug license. Further, this issue discusses the CDSCO alert of the risk of cybersecurity associated with the use of Medtronic insulin pumps. This issue then mentions the AYUSH Ministry’s research funding under EMR pro-gramme. Going forward, the current volume discusses the proposed 3rd amend-ment to Clinical Establishment Rules. Along with this information, this volume also covers an important patent injunction case between Natco Pharma and Bay-er’s group. Next is the discussion on the release of 2nd edition of Health Index fol-lowed by the news of Ghana FDA to adopt Indian Pharmacopoeia standards. This is followed by a description of WHO’s Prequalification Programme.

The volume then discusses the recent updates on Indian regulations in the health care sector presented as a separate section under Indian Health Care Highlights 2019.

From the international arena, the issue has a separate section which discusses re-cent US FDA updates for July 2019. Along with this, we have a separate new section for WHO updates as WHO Pharma Highlights July 2019.

Note: All reasonable precautions have been taken to verify the information con-tained in this publication. However, the published material is being distributed without warranty of any kind, either expressed or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall the author and/or the firm be liable for damages arising from its use.

Trust you enjoy reading this issue as well. Please feel free to send your valuable inputs / comments at [email protected]

Thank you.Contributors to the current issue: Mr. Manoj K. SinghMs. Vijaylaxmi RathoreMs. Arnika Sharma

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SINGH & ASSOCIATES ADVOCATES & SOLICITORS

NEW DELHI E-337, East of KailashNew Delhi - 110065 INDIA GURUGRAM7th Floor, ABW Tower, MG Service RoadSector 25, IFFCO Chowk, Gurugram Haryana - 122001 INDIAMUMBAI Unit No. 101, 10th Floor Sakhar Bhavan, Plot No. 230Ramnath Goenka MargNariman Point, Mumbai - 400021, INDIA, BENGALURU Condor Mirage, 101/1, 3rd FloorRichmond Road, Richmond TownBengaluru - 560025, INDIA

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Readers shall not act on the basis of the information provided in the Newsletter without seeking legal advice.

All ©Copyrights owned by Singh & Associates S&A Pharma Newsletter

Volume III, Issue VIIJuly 2019

2019 © Singh & Associates

www.singhassociates.in


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Managing Editor Manoj K. Singh

Published by Singh & Associates

Advocates and SolicitorsC

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ts1. Central Government bans use of Colistin in livestock to tackle anti- microbial resistance 4

2. The Drugs and Cosmetics (11th Amendment) Rules, 2019, offers effective implementation of permanency of licenses 5

3. CDSCO alerts on Medtronic insulin pumps for having potential cybersecurity risk 7

4. Ayush Ministry funds research projects in NCD as part of EMR programme 8

5. Health Ministry proposes Clinical Establishment (3rd Amendment Rules), 2019 9

6. Delhi High Court dismissed the petition of German drugmaker against Natco Pharma 11

7. NITI releases Healthy States Progressive India 2nd edition 12

8. Ghana FDA to adopt Indian Pharmacopoeia standards 14

9. WHO assures quality safety and efficacy standards of medical products by Pre-qualification Programme 15

10. India Healthcare Highlights July 2019 17

11. US FDA Highlights July 2019 19

12. WHO Pharma Highlights July 2019 21

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Central Government bans use of Colistin in livestock to tackle anti-microbial resistance

On July 19, 2019, the Central Government banned the manufacture, sale and distribution of Colistin and its formulations for food producing animals, poultry, aqua farming and animal feed supplements with immediate effect1. The regulatory measure was taken to ensure the cautious use of anti-microbial agents in humans and animals to tackle the issue of anti-microbial resistance.

The announcement follows the 81st Meeting of Drugs Technical Advisory Board (DTAB) held on November 29, 2018 which recommended the ban of colistin. The DTAB deliberated the representation received from Dr Abdul Ghafur, Coordinator, Chennai Declaration on Antimicrobial Resistance, which demanded an immediate ban of growing promotional use of Colistin in poultry and aqua farming.

The DTAB conducted a detailed examination of the matter with the Department of Animal Husbandry, Dairying and Fisheries (DADF), Ministry of Agriculture & Farmer’s Welfare and Food Safety and Standards Authority of India (FSSAI), MoHFW, has concluded that the use of Colistin as feed premix/feed supplement, is likely to involve risk to human beings.

Now, the Central Government in exercise of the powers conferred by section 26A2 of the Drugs and Cosmetics Act, 1940, and also agreeing with DTAB recommendation, has announced the immediate ban of Colistin for the use of promoting growth in livestock. in addition to the ban, the Government has also directed the manufacturers of said drug and its formulations to follow labelling requirement for the drugs and mention the words “NOT TO BE USED IN FOOD PRODUCING ANIMALS, POULTRY, AQUA FARMING AND ANIMAL FEED SUPPLEMENTS” in a conspicuous manner on the package insert and promotional literature.

About Colistin and AMRAntimicrobial resistance (AMR) is one of the top 10 global threats to human health, driven by the overuse of antimicrobials in people, and also in animals, especially those used for food production, as well as in the environment. As a result, standard treatments become ineffective, infections persist and may spread to others. Colistin is an antibiotic produced by certain strains of the bacteria Paenibacillus polymyxa. C. Colistin is effective against most Gram-negative bacilli and considered as a last resort drug for multidrug resistant gram-negative infections such as pneumonia and bacteremia in critically ill patients. Therefore, the WHO has marked Colistin as ‘Reserved’ antibiotic, and recommends to use it cautiously.

ConclusionBanning non-therapeutic use of colistin in animals is a significant step to tackle colistin resistance, which is part of Indian National Action Plan on AMR. And also a part of multisectoral approaches of Global Action Plan to address AMR.

1 http://www.egazette.nic.in/WriteReadData/2019/207345.pdf

2 Section 26A: Power of Central Government to prohibit manufacture, etc., of drug and cosmetic in public interest.— Without prejudice to any other provision contained in this Chapter, if the Central Government is satisfied, that the use of any drug or cosmetic is likely to involve any risk to human beings or animals or that any drug does not have the therapeutic value claimed or purported to be claimed for it or contains ingredients and in such quantity for which there is no therapeutic justification and that in the public interest it is necessary or expedient so to do, then, that Government may, by notification in the Official Gazette, regulate, restrict or prohibit the manufacture, sale or distribution of such drug or cosmetic.


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The Drugs and Cosmetics (11th Amendment) Rules, 2019, offers effective implementation of permanency of licenses

The Drugs and Cosmetics (10th Amendment) Rules, 2017 dated October 27, 20173, announced that the manufacturing and sale licenses of drugs once issued shall remain valid forever if the licensee deposits license retention fee every five years, unless the licenses are suspended or cancelled by the Licensing Authority. It also said that, in the case of manufacturing licenses, the premises shall be inspected jointly by the Central and State Drugs Inspectors at least once in three years or as required as per the risk-based approach. With this announcement, the provision of renewal of manufacturing and sale licenses was removed by the Government for ease of continuation of business.

Since then, the Government has received various representations from the State Licensing Authorities regarding certain anomalies in the published rules which were causing difficulties at the implementation level.

Now, therefore, the Central Government, on July 17, 2019, announced the Drugs and Cosmetics (11th Amendment) Rules, 20194 (“Amendment Rule”) for having effective implementation of permanency of drugs licenses for manufacturing and sale. The amendment brings the following changes in Drugs and Cosmetics Rule, 1945 (“Rule”):

A. THE BELOW PROVISIONS OF LICENSE RENEWAL/CERTIFICATES OF RENEWAL HAVE BEEN OMITTED BY AMENDMENT RULE:Rule 150J Renewal i.e., “On an application being made for renewal the approving authority may cause an inspection to be made and if satisfied that the conditions of the approval and the rules made under the Act are and shall continue to be observed shall issue a certificate of renewal in Form 38.”

Form 26J i.e., “Certificate of renewal of loan license to manufacture for sale of Large Volume Parenterals or Sera and Vaccine or recombinant DNA (r-DNA) derived drugs specified in Schedule C and C-1 excluding those specified in Schedule X”

Form 33 i.e., “Certificate of renewal of license to manufacture cosmetics for sale” is omitted in Rule 140 and Rule 143A.

Form 37 [Approval for carrying out tests on drugs/ cosmetics and raw materials used in their manufacture on behalf of licensees for manufacture for sale of drugs /cosmetics.] removes the words “or renewal” from its condition of approvals under Rule 150E.

Form 37 also removes the words “and any certificate of renewal in Form 38 [Certificate of renewal of approval for carrying out tests on drugs/ cosmetics and raw materials used in the manufacture thereof on behalf of licensees for manufacture for sale of drugs/ cosmetics]” from its condition to approval section.

B. THE PROVISIONS OF RENEWAL HAVE BEEN INCORPORATED IN FORM 24C I.E., ‘HOMOEOPATHIC MEDICINES’-Form 24C i.e., “Application for the grant or renewal of a license to manufacture for sale or for distribution of Homoeopathic medicines or a license to manufacture potentized preparations from back potencies by licensees holding license in Form 20C”

3 https://cdsco.gov.in/opencms/opencms/system/modules/CDSCO.WEB/elements/download_file_division.jsp?num_id=OTY4

4 http://www.egazette.nic.in/WriteReadData/2019/207196.pdf

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C. THE INSERTION OF RULE 77 AND RULE 82 TO ADD MORE CLARIFICATION REGARDING ‘DURATION OF LICENSES’: “77. Duration of license- A license issued in Form 28 [Schedules C and C (1)excluding X], Form 28B [Schedules C, C(I) and X] and Form 28D [Large Volume Parenterals/Sera and Vaccines/recombinant DNA (r-DNA) derived drugs Schedules C, C(I) and X] shall remain valid, if the licensee deposits a license retention fee before the expiry of period of every succeeding five years from the date of its issue, unless it is suspended or cancelled by the licensing authority.

If case of non-payment of license retention fee on or before the due date, the licensee shall be allowed to pay license retention fee along with a late fee (2% of retention fee every month) for the next 6 months, and in case of non-payment of such fee, the license shall be deemed to have been cancelled.”

“ 83. Duration of loan license- A loan license issued in Form 28 [Schedules C and C (1)excluding X], Form 28B [Schedules C, C(I) and X] and Form 28D [Large Volume Parenterals/Sera and Vaccines/recombinant DNA (r-DNA) derived drugs Schedules C, C(I) and X] shall remain valid, if the licensee deposits a license retention fee before the expiry of period of every succeeding five years from the date of its issue, unless it is suspended or cancelled by the licensing authority.

If case of non-payment of license retention fee on or before the due date, the licensee shall be allowed to pay license retention fee along with a late fee (2% of retention fee every month) for the next 6 months, and in case of non-payment of such fee, the license shall be deemed to have been cancelled.”

ConclusionThe amendment would ensure the smooth processing of applications for grant of manufacturing licenses and promote ease of doing business for drug manufacture and drug distributors.


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CDSCO alerts on Medtronic insulin pumps for having potential cybersecurity risk

On July 2, 2019, Central Drug Standard Control Organization (CDSCO) issued an alert for insulin pumps manufactured by Medtronic for its potential cybersecurity risk which can be a serious health hazard for the patient, as the insulin pump can be accessed and controlled by another person by compromising the cybersecurity.

Background of Cybersecurity RiskThe CDSCO alert is followed by the United States Food and Drug Administration (US FDA) warning letter, which said that certain Medtronic MiniMed insulin pumps are being withdrawn from market due to potential cybersecurity risks. However, no such reports of unauthorized persons changing settings or controlling insulin delivery has been confirmed. Now the alert issued by CDSCO clearly describes the risks associated with the use of the device. According to the CDSCO alert cybersecurity risk allows an unauthorized person with special technical skills to connect to a nearby insulin pump wirelessly, and then take control over the device and change its settings. Medtronic knowing the high cybersecurity risk associated with the device has published the ‘Field Safety Notification’ for patients’ awareness, which says:

y Keep your insulin pump and the devices that are connected to your pump within your control at all times. y Do not share your pump serial number. y Be attentive to pump notifications, alarms, and alerts. y Immediately cancel any unintended boluses. y Monitor your blood glucose levels closely and act as appropriate. y Do not connect to any third-party devices or use any software not authorized by Medtronic. y Disconnect your CareLink™ USB device from your computer when it is not being used to download data from

your pump. y Get medical help right away if you experience symptoms of severe hypoglycemia or diabetic ketoacidosis, or

suspect that your insulin pump settings, or insulin delivery changed unexpectedly.5

Insulin PumpsThe insulin pump delivers insulin to a patient throughout the day via a catheter implanted under the skin. This does away with need of injecting insulin injections at regular intervals to maintain stable blood glucose. They are designed in a way where they communicate using a wireless radio frequency (RF) with other devices such as a blood glucose meters, glucose sensor transmitters

ConclusionThe alert advised to all the patients using insulin pumps to slowly choose an alternate mode of medication, due to reports of cybersecurity risk associated with insulin pumps, and some of these devices have been withdrawn from the market. Hence, FDA has raised an alert to the patients and health care providers on the adverse event of cybersecurity risk with the device. This alert will help the diabetic patients at a global level and will promote safe medication options in treating diabetes.

5 https://cdsco.gov.in/opencms/opencms/system/modules/CDSCO.WEB/elements/download_file_division.jsp?num_id=NDU0MA==

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Ayush Ministry funds research projects in NCD as part of EMR programme

In order to increase the efficacy and role of herbal products in treating the prioritized diseases, the AYUSH ministry will fund research projects for the year 2019 in non-communicable disease (NCD) as a part of Extra Mural Research (EMR) scheme.

Background of EMR schemeAyurveda, Yoga & Naturopathy, Unani, Siddha, Sowa Rigpa and Homoeopathy offer a wide range of treatment options for various serious health issues. However, knowledge about the efficacy of herbal products is not wide spread especially on a global basis. AYUSH research council has been conducting research over last 40 years. Along with it many private institutions and universities have also contributed significantly to clinical research, ethno-botanical surveys, pharmacognostical and pharmacological studies on plants, and drugs standardization of simple and compound formulations used in Ayurveda, Siddha and Unani system of medicine. This research is not spread out globally; moreover, the public is equally concerned to know about the safety and efficacy of any new formulation or product. Hence, to overcome all such issues and encourage research and development in herbal products, AYUSH ministry along with the Government of India has introduced a scheme for Extra Mural Research to tap the potential of these organizations for the research needs of AYUSH sector. Under the scheme it will fund various research products in the field of Ayurveda and utilize the vast research infrastructure available within the country for standardization and validation of classical drugs.6

Under the EMR scheme all applicants can send their applications in prescribed format to the respective Research Councils of AYUSH in both hard and soft copies by July 20, 2019. The respective councils of AYUSH include Central Council for Research in Ayurvedic Sciences (CCRAS), Central Council for Research in Yoga and Naturopathy (CCRYN), Central Council for Research in Unani Medicine (CCRUM), Central Council for Research in Siddha (CCRS) and Central Council for Research in Homoeopathy (CCRH)7.

Non-communicable Diseases (NCDs)NCDs are categorized as diseases which are not passed from person to person and are typically of longer duration. The most common NCDs include cardiovascular diseases (such as heart attacks and stroke), cancers, chronic respiratory diseases (such as chronic obstructive pulmonary disease and asthma), and diabetes. As per the reports published by WHO, NCD kill 41 million people each year, equivalent to 61% of all deaths globally. NCD mostly affects the middle- and low-income countries. The high death rate due to NCD makes it very important to explore different ways of preventing the expansion of the disease. Hence, it is very important to find out different herbal remedies which can be effective in treating the disease effectively at a global level.

ConclusionAccording to WHO, non-communicable diseases cause 61% of deaths in India; hence, it has become very important to take all preventive measures to prevent the progression of such diseases. EMR scheme introduced by AYUSH ministry has taken charge to fund the organizations and private institutions conducting research work in the field of NCD and promoting the safety of the herbal products globally.

6 http://www.ayush.gov.in/sites/default/files/EMR%20Scheme.PDF

7 http://ayush.gov.in/sites/default/files/Advertisement_0.pdf


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Health Ministry proposes Clinical Establishment (3rd Amendment Rules), 2019

On July 17, 2019, the Health Ministry placed the draft notification on Clinical Establishment (Central Government) Third Amendment Rules, prescribing ‘minimum standards for different categories of Clinical establishments of Allopathy and AYUSH in public domain for comments/suggestions regarding8.

Background of Clinical Establishment RulesThe Clinical Establishment Act (‘Act’) was drafted in 2010 to provide registration and regulations to clinical establishments in the country that provide basic health amenities, the key feature of the Act being:

y Generation of the reliable database giving relevant information about all the clinical establishment overall the country,

y Classification of various clinical establishments based upon the categories and minimum standards, y Defining the minimum standards for all the clinical establishments, and y Assist the Government in obtaining information and data required from clinical establishments for public

health interventions including outbreak and disaster management.

At present minimum standards are only available for medical diagnostics labs, according to the Rule 8A as inserted in Clinical Establishments (Central Government) Amendment Rules, 2018:

Rule 8A of Act, says that “Minimum Standards for Medical Diagnostic Laboratories (or Pathological Laboratories) — Every clinical establishment relating to diagnosis or treatment of diseases, where pathological, bacteriological, genetic, radiological, chemical, biological investigations or other diag-nostic or investigative services, are usually carried on with the aid of laboratory or other medical equip-ment, shall comply with the minimum standards of facilities and services as specified in the Schedule.”9

Now, therefore the Health Ministry to bring uniformity in the standard of healthcare services provided by several establishments, has proposed for the third Amendment of Clinical Establishments (Central Government) Rules. The amendment proposes to set the minimum standards of the clinical establishment for Allopathy and AYUSH under Rule 8B of the Clinical Establishment Act, 2010. The Rule 8B states that:

Rule 8B: “Minimum standards Of Hindi and English versions of approved minimum Standards for fol-lowing categories of Allopathic Clinical Establishment”.10

Minimum Standards (General) of Clinical establishments as listed under:

y Clinic or Polyclinic: only Consultation, With Dispensary, With Diagnostic Support and With Observation facility y Mobile Clinic: Only Consultation’ With Procedures and Dental Mobile 3. y Hospitals: Level 1 to 3 y Health Check-up Centre y Dental Lab y Physiotherapy y Dietetics y Integrated Counselling Centre

8 https://mohfw.gov.in/sites/default/files/clinicalestablishment.pdf

9 http://clinicalestablishments.gov.in/WriteReadData/4161.pdf

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These set of common minimum standards are equally applicable to a single practitioner or more than one doctor clinic manned by a general physician or specialist doctor or super specialist or a group of doctors who are themselves providing patient care services like dispensing of medicines, injection and dressing.

ConclusionThe new amendment has been proposed in order to ensure registration and regulation of all the clinical establishments around the country. This will help in bringing uniformity in the healthcare sector so that public can approach the health facility with ease and they are given a standard treatment.


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Delhi High Court dismissed the petition of German drugmaker against Natco Pharma

On July 11, 2019, a division bench of Judges of Delhi High Court passed an order which clearly dismisses an injunction petition filed by German drug maker, Bayer group, to protect its drug Regorafenib sold under brand name Stivarga against Natco Pharma.11

Background of the caseThe Bayer Group (Plaintiff ) of Companies filed an injunction petition against Natco Pharma in a bid to stop the company from making, distributing, advertising, exporting, offering for sale and in any other manner directly or indirectly dealing with any product that infringes the subject matter of the Plaintiff’s Patent (Indian Patent No. 240207) or any claims thereof, including Regorafenib and any forms thereof. In the petition the plaintiff mentioned that the company was granted the patent for the drug Regorafenib on April 29, 2010. The drug Regorafenib covered in the patent is used in the treatment of metastatic colorectal cancer and advanced gastrointestinal stromal tumors. Earlier, on July 5, 2019, through a ruling, Bayer Group secured an injunction against Natco, followed which Natco Pharma appealed the judgement and the case was transferred to division bench of the Delhi High Court. The bench of judges reviewed the case and sent back the case to the Single Judge for hearing the matter afresh.

According to the order of the division bench:“The learned Single Judge in the impugned order does not set out any prima fascia view. On the con-trary. It records in para 912 that at this stage, it is not possible to form an opinion even prima fascia. As regards the other two elements, balance of convenience and irreparable hardship, there is no mention of these, even impliedly in the impugned order”13.

According to Natco Pharma, Regorafenib is already disclosed in an earlier patent filing and hence the new patent claims are not valid for protection.

Section 83 of the Patent Act, 1970, states that any “patent granted should not prevent public health and nutrition and should act as instrument to promote public interest specially in sectors of vital importance for socio-economic and technological development”. In response to this consideration Natco Pharma’s product is available at INR 9000 per bottle which is comparatively much lesser priced that Bayer’s products available at INR 36000 to INR 40000 per bottle. Natco Pharma had also agreed to provide the medicine free to 2000 patients for life. It had also filed a lawsuit in a Hyderabad court for such clarification. Bayer, on the other hand, filed its claims of patent infringement at Delhi High Court asserting its patent. However, the decision of Division Bench of Delhi High Court was strongly condemned and raised alert and controversies at an international level. There was an immense pressure from US lobbies and government agencies that alleged India had disregarded patent rights of global corporations and played a discriminatory policy favoring the local companies. India, however, maintained it had followed the WTO provisions and exercised flexibilities allowed in determining patent rules.

Conclusion The division bench court has sent the case back to the Single Judge of the Delhi High Court to thoroughly review the case and to examine the order which is favorable for both. The judge should also make sure the order should not suspend any laws of the Patent Act.

11 https://indiankanoon.org/doc/52483234/?type=print

12 https://www.livelaw.in/pdf_upload/pdf_upload-362155.pdf

13 https://www.livelaw.in/pdf_upload/pdf_upload-362155.pdf

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NITI releases Healthy States Progressive India 2nd edition

NITI Aayog and Ministry of Health and Family Welfare (MoHFW) has released the 2nd edition of health index “Healthy States, Progressive India” report14, which measures Indian states and union territories on the basis of their year-on-year incremental improvement in health and overall performance. The ranking is categorized as Larger States, Smaller States and Union Territories (UTs), to ensure comparison among similar entities.

The Health Index, developed by the trio group of NITI Aayog, World Bank, and MOHFW, helps in measurement of improvements in health, and will also guides the health agencies in strategizing their interventions to further improve the health outcomes in the coming years.

Health Index The Health Index is a useful tool to measure and compare the overall performance and incremental performances across States and UTs over time. The Health Index is a weighted composite index based on 23 indicators grouped into the domains of Health Outcomes, Governance and Information, and Key Inputs/Processes, submitted by States and UTs on the online portal maintained by NITI Aayog excepting 12 indicators which can be pre-filled as per its availability in the public domain. The data is then validated by an Independent Validation Agency (IVA) and is used as an input for the generation of Index values and ranks:

y Ranks - The ranks are generated according to three categories of States (Larger States, Smaller States and UTs) to ensure comparability among similar entities.

y Incremental Performance- Incremental performance measures the change in the Health Index score from Base to Reference Year, which is marked by the year-specific rankings based on the Index score. The States are categorized into four groups based on incremental performance - not improved (<=0 incremental change); least improved (0.01 to 2 points increase); moderately improved (2.01 to 4 points), and most improved (>4 points increase).

y Overall performance: Overall performance is measured using the composite Index scores for Base and Reference Years. The States are also categorized on the basis of Front-runners: top one-third, Achievers: middle one-third, Aspirants: lowest one-third.

Larger States on incremental performance and overall performance:Among the twenty one (21) Larger States, Kerala, Andhra Pradesh & Maharashtra ranked on top in terms of overall performance, while Haryana, Rajasthan and Jharkhand are the top three ranking States in terms of annual incremental performance from base to reference year in indicators such as Neonatal Mortality Rate (NMR), Under-five Mortality Rate (U5MR), Proportion Low Birth Weight among New-borns, Proportion of districts with functional Cardiac Care Units (CCUs), Proportion of ANCs registered within first trimester, Proportion of CHCs/PHCs with Quality Accreditation Certificates etc. The most significant progress in ranks has been observed in Andhra Pradesh followed by Rajasthan, improving their ranking by six and four positions respectively.

Bihar (ranked at the bottom) registered the most negative incremental change, and this is reflected in the deterioration of most health indicators such as TFR, LBW, SRB, institutional delivery, TB notification rate, TB treatment success rate, ANM and staff nurse vacancies, functional 24x7 PHCs, birth registration.

Smaller States on incremental performance and overall performance:Among eight (8) Smaller States, Mizoram ranked first followed by Manipur on overall performance, while Tripura, Nagaland followed by Manipur were the top ranked States in terms of annual incremental performance on indicators such as full immunization coverage, institutional deliveries, total Case Notification Rate of Tuberculosis

14 https://niti.gov.in/writereaddata/files/document_publication/NITI-WB%20Health%20Index%20Report%20%28Web%20Ver%29_11-06-19.pdf


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etc. While the remaining four States - Meghalaya, Goa, Sikkim, and Arunachal Pradesh registered a negative incremental change.

The indicators where most Smaller States need to focus include LBW, TB treatment success rate, average occupancy of State-level key positions, functional 24x7 PHCs, first trimester ANC registration and IDSP reporting.

UT on incremental performance and overall performanceAmong UTs, Chandigarh and Dadra and Nagar Haveli were ranked on top in terms of overall performance as well as annual incremental performance. These two UTs showed the highest improvement in indicators such as total Case Notification Rate of Tuberculosis, Average Occupancy of an officer (in months) for 3 Key State posts for last 3 years, proportion of ANMs positions vacant at sub-centers, proportion of staff nurses positions vacant at PHCs and CHCs, proportion of MO positions vacant at PHCs, proportion of total staff (regular and contractual) with e-pay slip generated in the IT enabled Human Resources Management Information System etc. Four UTs dropped in the ranking - Lakshadweep from first to third, Delhi from third to fifth, Andaman and Nicobar Islands from fourth to sixth, and Daman and Diu from sixth to seventh.

The indicators where most UTs need to focus include full immunization, average occupancy of State level key positions and District CMOs, filling vacancies of specialists at district hospitals, functional 24x7 PHCs and quality accreditation of public health facilities.

Note - The Health Index helps to understand the variations and complexities of the country’s performance in health. The first edition of Health Index had received a great response and initiated many fruitful discussions, including how to improve the data collection system to measure health performance, and how to promote positive competition and learning among the States and UTs. The current edition highlights the areas which require focus from States/UTs to improve their overall health outcomes/performance.

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Ghana FDA to adopt Indian Pharmacopoeia standards

On July 10, 2019, Indian Pharmacopoeia Commission declared that the Government of Ghana has given recognition to the Indian pharmacopoeia after continuous efforts of Central government in achieving the recognition15.

Background According to the resource information, Africa imports almost 70 percent of its drugs of which India makes a total contribution of around 55 to 60 percent. Moreover, Indian drugs are not only cost effective but also offer standard quality and have great potential and acceptance in various companies. Hence, to ease the process of drug import, the Ghana government planned to adopt India Pharmacopoeia. Based upon this, CDSCO, the highest regulatory body of India, supported and agreed to give a helping hand of Rupees 900 crore for training technical officers in Indian Pharmacopoeia along with improving the human resources, upgradation of laboratories, a training programme for regulator and revision of the Drug and Cosmetic Rule. The Indian Pharmacopoeia Commission has already submitted their application on January 16, 2017, to FDA Ghana with subject titled as “Recognition of Indian Pharmacopoeia Standards in Ghana” along with the letter from the High Commission of India. Prior to submitting this application Central Drug Standard Control Organization had agreed to provide the technical training to technical officers, helping in capacity building for drug testing and also to provide some basic standards necessary for drug testing.

Acceptance from FDA GHANAOfficials from the FDA of Ghana have accepted the proposal of Indian government and on July 10, 2019, have sent an acceptance letter to the Government of India. According to the officials from FDA Ghana, they do not reject any application containing an active pharmaceutical ingredient (APISs) and finished pharmaceutical products (FPP) controlled as per the Indian Pharmacopoeia. However, to undergo best regulatory practice, they have to perform the specification for Indian Pharmacopoeia with other officially recognized Pharmacopoeia like British Pharmacopoeia, US pharmacopoeia and International Pharmacopoeia. Any inadequacy found in APIs and FPP controlled as per the Indian Pharmacopoeia standards need to be addressed in order to comply with rules and standards of other officially recognized pharmacopoeia. Hence the FDA Ghana believes that Indian pharmacopoeia is an approved reference of the FDA when its monograph is compared with the monographs of the recognized pharmacopoeia.16

ConclusionAs per the source information the standards of the Indian pharmacopoeia are close to other officially recognized pharmacopoeia like British Pharmacopoeia, US pharmacopoeia and International Pharmacopoeia; hence, FDA of Ghana has decided to adopt Indian Pharmacopoeia due to standard quality and great potential and acceptance in various companies.

15 https://www.ipc.gov.in/news-highlights/655-recognition-of-indian-pharmacopoeia-by-flda-ghana.html

16 https://www.ipc.gov.in/news-highlights/655-recognition-of-indian-pharmacopoeia-by-flda-ghana.html


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WHO assures quality safety and efficacy standards of medical products by Pre-qualification Programme

Pre-qualification programme (PQP) a United Nations programme set up in 2001, facilitates the provision of list of prequalified essential medical products that meet unified standards of quality, safety, efficacy and performance. The programme is managed by the World Health Organization (WHO) with the support of UNAIDS, UNICEF, UNFPA and the World Bank. The programme mainly covers the medicines used to treat HIV/AIDS, tuberculosis, malaria, and reproductive health. The programme assesses medical products using a standard five point quantifiers, and once the product is found to be acceptable, the WHO prequalifies it for procurement by UN agencies such as UNICEF, the Global Fund to Fight AIDS, Tuberculosis and Malaria, and UNITAID – for further distribution of these products in resource-limited countries.

The medical products including in-vitro diagnostics (IVDs), active pharmaceutical ingredients (APIs), finished pharmaceutical products (FFPs), immunization devices, vaccines and Medicines quality control laboratories (QCLs) for chemical and microbiological testing of medicines are examined under this programme.

Eligibility to apply for WHO Pre-qualificationAny manufacturer shall be eligible by submitting an Expression of Interest for Product Evaluation (EOI) to WHO for prequalification. But prior to submitting a medical product for an EOI, it shall need to qualify one or more of the following three criteria: 1) It is listed on the WHO Model List of Essential Medicines; 2) An application for inclusion to the Model List has been submitted to the relevant WHO Expert Committee for assessment; and 3) It is recommended for use by a current WHO treatment guideline. At present, medical products related to the following therapeutic areas are considered to submit an EOI for Pre-qualification, namely:

y Diarrhoeal disease y Hepatitis B and C y HIV/AIDS y Influenza y Malaria y Neglected tropical diseases y Reproductive health and y Tuberculosis

The pre-qualification process17

Pre-qualification process involves five major components - invitation, dossier submission, assessment, inspection, and final decision.

I. Invitation: The WHO’s PQP issues an invitation to manufacturers to submit an EOI for product evaluation. Only products included in an EOI are eligible for pre-qualification.

II. Dossier submission: The manufacturer provides a comprehensive set of data about the quality, safety and efficacy of the product submitted for evaluation.

III. Assessment: A team of experts from national regulatory authorities worldwide and WHO staff evaluates all the data presented.

IV. Inspection: An inspection of the manufacturing sites for the medical products shall be conducted to check its compliance with WHO Good Manufacturing Practice (GMP). They also verify that any contract research organization that conducted any clinical studies relating to the submitted product complies with WHO good clinical practice and WHO good laboratory practice.

V. Decision: If the product is found to meet the specified requirements, and the associated manufacturing site(s)

17 https://www.who.int/diagnostics_laboratory/en/

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and contract research organization(s) are compliant with WHO standards, the product is added to the WHO list of prequalified medicinal products.

The duration for the entire pre-qualification process varies from case to case basis, it can take as little as three months or extend to a few long years, provided the data submitted is complete and complies with all required standards.

Post-prequalification ProcessOnce the medical product is prequalified (APIs, FFPs, QCLs, and IVDs), it undergoes for the quality verification process to ensure its constant quality over time. The verification is conducted via:

y Monitoring and/or review of amendments to API master files and variations to FPPs depending on the degree of risk associated with the changes, or which could affect the ongoing quality and safety of an API, or the safety, quality and efficacy of an FPP.

y FPP requalification is observed after every five years of pre-qualification, or when requested to do so by WHO, which requires a prequalified FPP to submit data and information to WHO for requalification assessment.

y Reinspection of API and FPP manufacturing sites, and of QCLs either routinely or in follow up to receipt of a complaint.

y Quality monitoring surveys, field sampling and testing projects are carried out randomly to monitor the quality of medicines or in follow up to receipt of a complaint.

y Monitoring of the quality of services provided by prequalified QCLs through review of updated Laboratory Information.

Note - WHO-prequalification process provides accelerated access to prequalified products in many countries with limited regulatory resources, stringent regulatory authorities, and where the products are yet to be regis-tered and can take considerable time. In this situation WHO, by collaborative efforts, can create procedures to accelerate the national registration process for timely access of prequalified products to that country.


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India Healthcare Highlights July 2019

This segment of the newsletter shares recent information associated with regulatory reforms from Healthcare and Pharmaceutical sectors from in Indian jurisdiction. This segment collates information on a monthly basis via conducting research and appraisal of applicable statutory provisions. Below are the highlights for July 2019:

No timeline for Finalization of Draft Rules on Sale of Drugs by e-Pharmacies18

On June 25, 2019, the Minister of State (Health and Family Welfare), in a written reply in the Rajya Sabha informed the status of finalizing ‘Draft Rule’ on Sale of Drugs by e-Pharmacies. Earlier, the Government, on August 28, 2018, had proposed the draft rules for incorporating provisions relating to the regulation of online sales and distribution of drugs in Drugs and Cosmetics Rule, 1945. A large number of suggestions/ comments received from the public/stakeholders in this matter are under examination, at the same time it is also sub judice before various Hon’ble High Courts in the country. Therefore, the Health Ministry stated that no timeline for finalization of the rules can be provided as of date.

While the ‘Draft Rule’ is yet to finalized, the Health Ministry directed State Licensing Authorities to take appropriate action under Drugs & Cosmetics Act if the sale of spurious drugs and violation of Act & Rule is reported in their jurisdiction.

World Bank supports “Treat and Eliminate Tuberculosis from India” program19

On June 27, 2019, the World Bank and the Government of India (GOI) signed a loan agreement of $400 Million to expand and speed up the interventions for the control of Tuberculosis (TB), which predominantly affects the underprivileged and marginalized population and kills almost half million people every year in India. The program aims to cover nine States of India via:

y Strengthening the diagnostics and management system of drug-resistant tuberculosis and capacity buildings of public institutions which are involved in TB management in the country.

y Ensure that private sector providers adhere to established protocols of timely diagnosis, notification and effective management of TB.

y Provide financial incentives to private care providers for reporting cases and ensuring high adherence to the treatments.

y Provide Direct Benefit Transfers to patients for acquiring the critical nutrition needed during treatment. y Strengthen ‘Nikshay program’, which is a web-based TB case monitoring system introduced by the GOI.

Ministry of Electronics and Information Technology signed MOU with AYUSH20

On June 30, 2019, an MoU was signed between Ministry of AYUSH (MOA) and Ministry of Electronics and Information Technology (MeitY) for the digitization of AYUSH Sector. According to this MoU, MeitY will provide technical support to MOA for planning and development of AYUSH GRID Project. AYUSH, in pursuance to the National Health Policy 2017 and e-governance initiative, aims to digitize the entire field of health care delivery at all levels, and also for more significant research, education, delivery of various healthcare programmes and better drug regulations. Overall the MOU will help AYUSH to get the high quality technical support from MeitY for digitalization of AYUSH Ministry.

18 http://pib.nic.in/PressReleseDetail.aspx?PRID=1575553



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CCMB and CDFD collaborate to address the Genetic Disease burden of the Indian population21

On July 03, 2019, an MoU was signed between Centre for Cellular and Molecular Biology (CCMB) and Centre for DNA Fingerprinting and Diagnostics (CDFD); both are premier national institutes of CSIR involved in the cutting-edge biological research in the field of Genetics with rapid advancements in technology. Genetic disorders form a major group of the non-communicable diseases and third most frequent cause of mortality in neonates in the country. It is estimated that almost half a million babies are born with genetic diseases every year. The burden of these disorders is a threat for the society, as most of these disorders are presently untreatable and those which are treatable are very expensive. The preventive approach is the only available option to manage these disorders, which requires prenatal diagnosis and genetic counselling.

The MoU aims to maximize the potential of both the institutes in human disease diagnostics via quality DNA based diagnostic services to the public at lower costs, to develop newer diagnostic methods and to engage in scientific research to improve understanding of human genetic disorders. It also aims to conduct training and educational activities on Genetic Diagnostics in both the institutes.

Cabinet approves MoU between India and Maldives in the Health Sector22

On July 03, 2019, the Union Cabinet has given ex-post-facto approval to the Memorandum of Understanding (MoU) between the Government of India and the Government of the Republic of Maldives on cooperation in the field of Health signed on June 08, 2019. The MoU covers the following areas of cooperation - Exchange & Training of medical doctors, officials, other health professionals and experts, Medical and health research development, Regulation of medicines and medical products and exchange of information thereon, Communicable and Non-Communicable diseases, E-Health and Telemedicine and any other area of cooperation as may be mutually decided upon.

21 http://pib.nic.in/PressReleaseIframePage.aspx?PRID=1576963



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US FDA Highlights July 2019

This segment discusses the recent drug approvals from the US FDA in various severe diseases. The write-ups describe the role of a new drug in the treatment of serious conditions such as myeloma, optical disease, and rhinitis. The FDA is the strongest regulatory body in USA which takes care of health of the public by assuring the safety and effectiveness of the human drugs, medical devices and other products used in health care.

FDA approves new treatment for refractory multiple myeloma23

On July 3, 2019, the U.S. Food and Drug Administration (U.S. FDA) approved Xpovio (selinexor) tablets in combination with the corticosteroid dexamethasone for the treatment of adult patients with relapsed refractory multiple myeloma (RRMM) resistant to different forms of treatment. Prior to the drug selinexor, the treatment option available to a patient with relapsed refractory multiple myeloma only used to slow down the spread of cancer. It was a very exhaustive process. Multiple myeloma, also referred to as plasma cell myeloma, is a cancer that begins in plasma cells (white blood cells that produce antibodies).

Xpovio is an orally available, small-molecule inhibitor of CRM1 (chromosome region maintenance 1 protein, exportin 1 or XPO1), with potential antineoplastic activity. Efficacy of the drug was studied in 83 patients with RRMM treated with Xpovio in combination with dexamethasone, which was effective in treating serious conditions. The FDA granted the approval of Xpovio to Karyopharm Therapeutics.

FDA warns re-packers of API for violating Good Manufacturing Practice24

On July 2, 2019, U.S. Food and Drug Administration (U.S. FDA) issued warning letters to three re-packers of active pharmaceutical ingredients (API) - B&B Pharmaceuticals, Inc. and Asclemed USA, Inc., doing business as Enovachem and Spectrum Laboratory Products, Inc., for significant violations of current good manufacturing practice (CGMP) requirements. U.S. market is the safest market as it has strict regulatory guidelines and protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. However, due to globalization and unauthorized deals in the pharmaceutical sector, there is an increasing threat to the quality of drug manufacturing.

FDA approves the first treatment of neuromyelitis optica spectrum disorder (NMOSD)25

On June 27, 2019, the US FDA approved Soliris (eculizumab) injection for intravenous use for the treatment of neuromyelitis optica spectrum disorder (NMOSD), a rare autoimmune disease of the central nervous system in adult patients who are anti-aquaporin-4 (AQP4) antibody positive. In patients with NMSOD, the body’s immune system mistakenly attacks healthy cells and proteins in the body, most often in the optic nerves and spinal cord resulting into the attack of optic neuritis, eye pain and vision loss. Soliris is a monoclonal antibody that targets complement protein C5, preventing cleavage to C5a and C5b, and the formation of the terminal complement complex C5b-9. Inhibition of this complex prevents complement mediated intravascular hemolysis in paroxysmal nocturnal hemoglobunuria, complement mediated microangiopathy in atypical hemolytic uremic syndrome, and immune mediated inflammation and damage of the central nervous system in neuromyelitis optica spectrum disorder. The efficacy of the drug was studied in a clinical study of 143 patients with NMOSD who had antibodies against AQP4 (anti-AQP4 positive) who were randomized to receive either Soliris treatment or placebo. Compared to treatment with placebo, the study showed that treatment with Soliris reduced the number of NMOSD relapses

23 https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-refractory-multiple-myeloma

24 https://www.fda.gov/news-events/press-announcements/fda-warns-repackers-distributing-pharmaceutical-ingredients-including-opioids-putting- consumers-risk

25 https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-neuromyelitis-optica-spectrum-disorder-rare-autoimmune- disease-central

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by 94 percent over the 48-week course of the trial. The FDA granted the approval of Soliris to Alexion Pharmaceuticals.

FDA approves the first treatment for chronic rhinosinusitis with nasal polyps26

On June 26, 2019, US FDA approved Dupixent (dupilumab) to treat adults with nasal polyps (growths on the inner lining of the sinuses) accompanied by chronic rhinosinusitis (prolonged inflammation of the sinuses and nasal cavity). Nasal polyps is a disease which can lead to loss of smell which can often require surgery to remove the polyps. Dupixent Dupilumab is a recombinant human IgG4 antibody to the IL-4 receptor that works by inhibiting the activation of certain pro-inflammatory cytokines that are implicated in the pathophysiology of several allergic and atopic conditions, including asthma, chronic rhinosinusitis with nasal polyps, and food and environmental allergies. The efficacy and safety of Dupixent were established in two studies with 724 patients, 18 years and older with chronic rhinosinusitis with nasal polyps who were symptomatic despite taking intranasal corticosteroids.

26 https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-chronic-rhinosinusitis-nasal-polyps


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WHO Pharma Highlights July 2019

This segment of the newsletter is focused on sharing the recent regulatory reforms and updates on Healthcare and Pharmaceutical domain from the World Health Organization (WHO). This segment collates information periodically via conducting research and review of pharmaceutical updates from the WHO. Below are the highlights for July 2019:

WHO releases Essential Medicine/ (in vitro) Diagnostics lists 201927

WHO, to prioritize critical health products available at an affordable price throughout health systems worldwide, has released the Essential Medicines List (2019) and the List of Essential (in vitro) Diagnostics. These two lists mainly focus on the major global health challenges like cancer and infectious diseases. Both the lists form the reference list for the countries to develop their own nationalized lists. They also provide a framework for the regulators to improve their laboratory services and medicines as per global standards.

The updated Essential Medicines List incorporates 460 products with adds on of 28 medicines for adults, 23 for children, and extended indication for 26 already-listed products. Whereas, the updated version of Essential Diagnostics List contains 46 general tests that can be used for routine patient care as well as for the detection and diagnosis of a wide array of disease conditions, and 69 tests intended for the detection, diagnosis and monitoring of specific diseases.

WHO prequalifies the first drug for Hepatitis C and First Self-test for HIV28

World Health Organization (WHO), to assure quality, safety and efficacy of priority medicines, has prequalified the first generic version of Sofosbuvir, 400 mg tablet, a direct-acting antiviral medicine for the treatment of Hepatitis C manufactured by Mylan Laboratories Ltd., India. Sofosbuvir (Sovaldi) developed by Gilead remains highly expensive in many countries, but licensing agreements between developing company and a number of generic manufacturers have made it more affordable for the low-income and middle-income countries. The prequalification of Sofosbuvir would expand its access by providing quality-assured generic medicines on the market.

Besides, the WHO also prequalified the first OraQuick ® HIV Self-Test to increase HIV diagnosis and treatment. The product is manufactured by OraSure Technologies Inc., which uses the oral fluid as a specimen and provides results in as little as twenty minutes. In 2016, an estimated 30% of all people living with HIV remained unaware of their HIV status, whether due to social stigma or less likely attitude to approach a health care facility or were unable to do so by the high risk population

27 https://www.nhp.gov.in/NHPfiles/WHO%20Classification.pdf

28 https://www.who.int/medicines/news/2017/1st_generic-hepC_1stHIVself-test-prequalified/en/

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July 2019Vol. III, Issue VII

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