data in÷teg÷ri÷ty: time to integrate human factors

Data In÷teg÷ri÷tyAJAZ S. HUSSAIN, PH.D.| INSIGHT, ADVICE & SOLUTIONS LLC

2/7/2014 [email protected] 1

Current Situation: CGMP, India & USA

• Remediation poses several challenges. How to understand why?

Poor data integrity practices noted by US FDA & UK’s MHRA at several companies in India

• Understanding human behavior is critical . What may be the root cause of noted ‘cluster’ of challenges?

It has bee alleged that “Chalta-Hai” attitude etc., are part of the cause…



• Reason for optimism. It is already happening.

Both US and UK regulators have acknowledged that many companies in India state-of-the art

• Signal standard will take time . How to move in this direction and create a win-win opportunity?

Authorities in India have expressed displeasure on the notion of dual standards



• Appreciating differences in each others needs. Opportunities at hand to improve affordability.

Suspicion of ‘political and business interest’ raise the possibility of unease in bilateral relations

• Delivering affordable high quality for all - Training, technology and trust.

It is time to turn the corner by getting to the root cause and work to fill the divide


Integrity of dataSurvey question 1:

Key attributes of data quality necessary for assurance integrity?

(select all correct answers)

A. Contemporaneous

B. Accurate

C. Attributable

D. Original

E. Long-lasting

An illustrative list of observations (FDA 483)

During inspection of your firm we observed

• “…trial injections…..”

• “…results failing specifications are retested until acceptable results are obtained….”

• “…over-writing electronic raw data…..”

• “…OOS not investigates per XYZ SOP”

• “…appropriate controls not established….”

• “….records are not completed contemporaneously”

• “…observed analyst back-date logbooks”


CAPA: Unacceptable to acceptable


PastBehavior

FutureBehavior

CAPA

Change in antecedents to past & current behavior?

Past behavior:

“…results failing

specifications are retested

until …”

Attitude towards the behavior?

Subjective norm?

Perceived behavioral

control?

Current behavior:

“…results failing

specifications are retested

until …”


Correcting past poor data integrity practices …

High stakes

High risk (legal, reputational, financial..) at individual &

organizational level

Interdependence

Pooled, sequential and reciprocal dependencies

across the enterprise

Complexity

Interrelated goals, large number of sub-tasks, high

information density


A useful analogy is the concept of ‘Risky Trust’ proposed by Faaiza Rashid and Amy C. Edmondson. Risky Trust: How Multi-entity Teams Develop Trust in a High Risk Endeavor . Working Paper 11-089. 2011, Harvard Business School.

Building this – “Risky Trust”• Intentions

• Competence, and

• ProcessTrust Dimensions

• Leader framing,

• Team member interactional expertise,

• Procedural transparency and impartialityAntecedents

• Monitoring behaviors (authorized peer pressure and continuous co-validation)

• Learning behaviors (swift corrective action and adaptive problem solving)

Behaviors


Faaiza Rashid and Amy C. Edmondson. Risky Trust: How Multi-entity Teams Develop Trust in a High Risk Endeavor . Working Paper 11-089. 2011, Harvard Business School.

Three areas that need a added emphasisTrust

dimension:

Intentions

Antecedents:

Leader framing

Behaviors:

Learning behaviors (swift corrective action

and adaptive problem solving)


Key challenges: Leader framingLeader framing

◦ Poor data integrity practices have been noted by US and UK regulators (the same observation were not necessarily noted by their Indian counterparts)

◦ From the US perspective - procedural adherence, documentation, and testing are critically necessary for assurance of product quality; not doing so results in the product to ‘adulterated’

◦ In the Indian regulatory system word ‘adulterated’ is defined differently

In a report (http://www.livemint.com/)dated 26 August 2013 the CEO of this Indian Company explained…

“The meaning of the word adulterated was very different in the US compared to the dictionary meaning as understood by people or even as defined under the Indian Drugs and Cosmetics Act.”


http://www.livemint.com/

Drug Manufacturing Focus: Why India?


Siegfried Schmitt. PHARMACEUTICAL TECHNOLOGY. Volume 37, Issue 12, pp. 58 (Dec 2, 2013).

“Though there is no denying that data-handling irregularities have been detected, there has not always been a malicious intention behind them.”

“In several cases, there has been a misguided belief that data should look good.

However, such data manipulation or data invention still constitutes fraud, irrespective of a person’s intention.”

http://www.pharmtech.com/pharmtech/author/authorInfo.jsp?id=39704

Would you give the benefit of doubt* and categorize this observation as an misguided?

“….records are not completed

contemporaneously”

Misguided

Malicious


*Sometimes the desire to have visually clean (without smudges) records can be the explanation; but the body language - fear and stress of an inspection – conveys the opposite impression.

How about now?


contemporaneously”

“…observed analyst back-date logbooks”

Misguided or malicious


And now?

Misguided or malicious

“appropriate controls not established.”

“…observed analyst back-date

logbooks”


contempor-aneously”


If observations are arranged in this sequence?

“…appropriate controls not established….”

“….records are not completed contemporaneously”

“…over-writing electronic raw data…..”

“…trial injections…..”

“…results failing specifications are retested until acceptable results are obtained….”

“…OOS not investigates per XYZ SOP”


Do you agree?Survey Question 2:

“Jugaad, coupled with the attitude of “chalta-hai” in an environment that rewards absolute conformity to hierarchy and greed eventually leads to fraud.” Dinesh Thakur June 19, 2013.

“Does India have cultural issues?” [compliance with US FDA requirements]

A. No

B. Yes a. Shop-floor

b. Supervisors

c. Middle managers

d. Senior management

e. All levels

http://www.thehindubusinessline.com/opinion/our-propensity-for-jugaad-comes-in-the-way-of-developing-quality/article5620563.ece


http://www.thehindu.com/opinion/op-ed/dinesh-thakur-responds/article4827458.ece



Do you agree?Survey Question 3:

“Scientists and operators were incentivized to act in a manner that produced results desired by the management by whatever means necessary.” Dinesh Thakur January 26, 2014

What % of companies you believe do so?

A. 0%

B. Less than 10%

C. Between 10 -20%

D. Between 20 -30%

E. More than 30%



Caution – potential for a ‘framing effect”

The range A (0%) - E (>30%) is arbitrary.

Ensure the choice of this range does not influence your answer.



We have already used terms such as…• a determination to act in a certain wayIntention [इरादा]

• a state or habit of mind in which trust or confidence is placed in some person or thingBelief [विश्िास]

• led or prompted by wrong or inappropriate motives or idealsMisguided [पथ से भटका हुआ]

• intentional perversion of truth in order to induce another to part with something of valueFraud [छल/कपट/धोखा ]

• literal translation ‘it moves’ - often expresses an attitude of ignoring rules because of a belief that they are not important (“it will do”) “Chalta-hai” [चलता है]

• a frugal solution or innovation (with a undertone of disregarding rules)“Juggad” [जुग्गद]


http://www.merriam-webster.comhttp://www.shabdkosh.com

http://www.merriam-webster.com/

http://www.shabdkosh.com/

Lets add a few more ….• the way a person or animal acts Behavior [बतााि]

• the way you think about or understand someone or something; the ability to understand or notice something easilyPerception [अनुभि]

• an individual’s perception of social normative pressures, or relevant others’ beliefs that he or she should or should not perform such behavior

Subjective norm [आत्मननष्ठ,

व्यक्ततपरक]

• to have power over (something); to cause (something) to act or function in a certain wayControl [काबू में रहना]

• To proceed objectively we need a precise definition….Misconduct [दरुाचार]


http://www.merriam-webster.comhttp://www.shabdkosh.com

http://www.merriam-webster.com/

http://www.shabdkosh.com/

Behaviors and antecedentsPast behavior

Attitude towards behavior

Subjective NormsPerceived behavioral

controlIntention Future behavior

Shop-floor

Supervisor

Middle Management

Senior Management

Shareholders

Regulators (local)

Regulators (aboard)

Media

Health care providers

Patients


Attitude towards the behavior

Subjective norm

Perceived behavioral control

IntentionFuture

Behavior

usually found to predict behavioral intentions with a high degree of accuracy

intentions, in combination with perceived behavioral control, can account for a considerable proportion of variance in behavior.

Ajen, I. The theory of planned behavior. ORGANIZATIONAL BEHAVIOR AND HUMAN DECISION PROCESSES 50, 179-211 (1991)

PastBehavior

Based on recent media reports* would this be a useful representation?

“chalta-hai”

Juggad

absolute conformity to

hierarchy

Please the supervisor

Repeat of FDA 483

As noted in FDA 483


*see previous slide; Survey questions 2 & 3

I don’t entirely think so; why?•There is generally high degree of

professionalism and the recognition of proper context & cultural undertones conveyed by such terms

Generalization to the sector would not be based on facts

•Of staff is certainly an aspect in need for attention

Training & Empowerment

•Would need to consider the element of ‘risk perception’

More apt representation?


Attitude towards the

behavior

Subjective norm

Perceived behavioral

control

IntentionFuture

Behavior

PastBehavior

Risk Perception

Then what may be the root cause of noted ‘cluster’ of challenges?Although there are similarities in poor data integrity practices noted across several companies specific root-causes would need to be investigated based on facts on ground

As noted previously (Siegfried Schmitt, December 2013) - there has not always been a malicious intent and there are misguided beliefs; these point to a need to further evaluate the attitudes and subjective norms in this context to ensure effective corrections

Clearly, like any where else, the possibility of malicious intent needs to be thoroughly investigated and appropriately disciplined not just by the organization but broadly; mechanisms for the letter (e.g., as available to the US FDA) are not apparent today


http://www.pharmtech.com/pharmtech/author/authorInfo.jsp?id=39704

[Non-malicious] Intention?

attitude toward performing the

behavior

the degree of positive negative evaluation of the

behavior

unpleasant-pleasant, unwise-wise, bad-good,

unnecessary-necessary,..

Validation is done so quality is good;

documentation not critical; test prone

to error

the subjective norm

perception that important others

think that one should or should

not..

"People who are important to me think I should do

XYZ

Supervisor would think batch failure

is my mistake

ALBARRACIN, JOHNSON, FISHBEIN, AND MUELLERLEILE Psychological Bulletin 2001, Vol. 127, No. 1, 142-161


It is often not understood thatCompendial standard (testing) is applicable to “units tested”

USP General Notices: 34th Revision: The similarity to statistical procedures may seem to suggest an intent to make inference to some larger group of units, but in all cases, statements about whether the compendial standard is met apply only to the units tested. Repeats, replicates, statistical rejection of outliers, or extrapolations of results to larger populations, as well as the necessity and appropriate frequency of batch testing, are neither specified nor proscribed by the compendia.


An additional influence?

Subjective norms

The focus is mainly on ensuring the final product

meets tolerance zones.

“The DCGI standards are lower but can we as a nation invest on each

facility at par with USFDA standards?”

“The almost doubling of costs is something we need to factor in.” Praful Akeli . Surabhi , Abantika Ghosh.

Jan 28 2014

the fact that facilities have failed

to meet FDA standards does not necessarily mean

the company's drugs are ineffective


http://www.financialexpress.com/news/jolted-by-us-ban-indian-regulators-wake-up-to-review-ranbaxy-laboratories-units/1221173

Almost doubling of cost due to increase in?

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Doing it right should not add cost as projected

Improved quality assurance

Diminishes perception of domestic vs. export quality

Pride and confidence

Support India’s aspiration to be the ‘pharmacy to the world’

US FDA is actively addressing these challenges

India has a tremendous opportunity to lead with existing center of excellence

Many companies in India have already moved forward

Quality by Design

• Punjab University has won the AAPS QbD Awards

Technological improvements

• IIT’s and NIPER


Clear path forward must be win-winIf I follow US standards, I will have to shut almost all drug facilities: G N Singh. Interview with Drug Controller General of India. Sushmi Dey January 30, 2014

We are going to insist that they don’t have any dual standards for international and Indian markets,” G N Singh, Drugs Controller General of India. Aesha Datta. January 27, 2014.


http://www.business-standard.com/article/economy-policy/if-i-follow-us-standards-i-will-have-to-shut-almost-all-drug-facilities-g-n-singh-114013000034_1.html

http://www.thehindubusinessline.com/companies/dual-standards-not-acceptable-indian-regulator-to-ranbaxy/article5623776.ece


• Appreciating differences in each others needs. Opportunities at hand to improve affordability.

Suspicion of ‘political and business interest’ raise the possibility of unease in bilateral relations

• Delivering affordable high quality for all - Training, technology and trust.

It is time to turn the corner by getting to the root cause and work to fill the divide
