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TheValidation Master Plan

Reasons, Regulations, and Rules:A Guide to the Validation MasterPlan (VMP)

Reasons, Regulations, and Rules:A Guide to the Validation MasterPlan (VMP)

T

by Brian W. Saxton

This articledescribes theelementalrequirements ofa ValidationMaster Plan(VMP), what it

should look like,what level ofdetail should beincluded, andFDAexpectations.

The US Food a nd Dr ug Administrat ion

(FD A) ha s been explicit in th e need for

valida tion, but implicit on th e elements

of that program. The chanting of the th ou sha l t

val idate mant ra is heard throughout the Drug,

Biologics, and Medical Devices sections of theCode of Federal Regulations (CFR), but, alas,

th ere is no boilerplat e templat e to follow . Orga -

nizat ions are t hus left to interpret th e regula-

tory requirements a nd craft individual program s

to comply. Is th ere a guiding principle tha t can

be applied here, to help companies distill rea ms

of mind-numbing regulations into elemental

val idat ion requirements?

An a dage a bout public speaking says t here

a re thr ee keys to a successful presenta tion:

1. Tell them wh at youre going to say .

2. S a y it .

3 . Tell them wha t you sa id .

This a da ge, in a slight ly modified form, can be

used to describe the ma jor elements of a Valida -

t ion Program:

1. Tell them w ha t youre going to do.

2. D o it .

3 . Tell them what you d id.

This t hree-step outline is a great ly simplified

model of the multitude of tasks a ssociat ed with

a va l idat ion progra m, but is an a ccura te sum-

ma ry of th e goals of each step of th e process. The

role of the Valida tion Mast er Pla n is to help an

organizat ion get i ts arms around a project-

specific valida tion effort by sett ing t he scope by

which a l l subsequent documents sha l l be

bounded.

To see how the parts of the validation pro-

gram fit into this modified adage, lets briefly

review the elements. Validation Program is

an umbrella t erm, encompa ssing a ll of the com-

ponents below - Tabl e A .

Validation Master Plan (VMP)The VMP serves as the val idat ion roadmap,

setting t he course, justifying t he stra tegy, out-lining the preliminary test and acceptance cri-

teria , a nd documenting the necessary programs

tha t ensure a continuing sta te of val idat ion.

QualificationThe Qualification phase provides documenta-

t ion that equipment and ut i l i ty systems were

insta lled properly thr ough an In sta llation Quali-

ficat ion (IQ), opera te correctly t hrough a n Op-

erat iona l Qua lification (OQ), a nd perform effec-

tively t hrough a P erforma nce Qualification (P Q).

Qual i f icat ion a ssures that the cri teria set forth

in the B asis of Design documents generated a t

project inception have been met in the fieldinstal lat ion.

Process ValidationB uilding on the da ta genera ted from the Qua l i-

fication pha se, the Pr ocess Va lidat ion (P V) pha se

focuses on the reproducibility of the systems

used and the resulting product quality. This

program challenges the ability of the systems

used (methods, equipment, and operators) to

meet th e pre-approved design intent .

Final ReportsFinal Reports (FR) compare the conclusions of

data gathered to the acceptance cri teria out-lined in th e Qualifica tion and Va lidation phases.

They determine the pa ss/fail sta tus a nd a d-

dress th e resolution of any devia tions. They a lso

can be referred to as S umma ry Reports .

Compliance ProgramsThe Validation program must ensure policies

an d procedures comply w ith current Good Manu-

facturing Pract ices (cGMP). Systems such as

cal ibrat ion, preventat ive ma intenance, chan ge

control, and revalidation contribute to a con-

t inuous stat e of val idat ion.

www.ipsdb.com

engineer ing

design/build

complian ce

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2 PHARMACEUTICAL ENGINEERING MAY/JUNE 2001

heValidation Master Plan

Considering the above, we can now complete the Valida-

t ion Program adage:

1. Tell them w ha t youre going to do (VMP).

2. Do it (IQ/OQ/P Q/P V).

3. Tell them wh at you did (FR).

This a rt icle w ill focus on the Tell them w ha t youre going to do

part of the Val idat ion P rogram, otherw ise know as t he Val ida-

t ion Ma ster P l an.

Planning OverviewThe purpose of th e VMP, in a prospective or concurrent va lida-

tion effort, is to explain the validation rationale associated

with the insta l lat ion, s ta rt-up, and use of a new production

line. This ra tionale should review ma nufa cturing systems a nd

assess t he potential of each to a ffect end-product qu ality . The

new process may be as simple as an accessory change on

existing product equipment , or a s complex as a new building

wit h a ll new utilities an d equipment. The size and scope of theproject d etermines th e size and scope of th e resulting VMP . For

a retrospective validation effort, the VMP documents the

existing production line and outlines the an ticipat ed test an d

an a lytical m ethodologies to be employed.

The VMP should be aut hored for its au dience, including t he

organizat ions qual i ty , engineering, and regulatory depart-

ments, th e FDA, a nd potential outside contra ctors. Ea ch group

looks for di fferent elements. Outside contractors want a

Deliverables List on wh ich t o base quotes an d define the scope

of work; the FDA looks for the pre-approved intention to

comply wit h Federa l regulat ions; w hile in-house qua lity, engi-

neering, and regulatory departments look for an accurate

representation of systems and corporate policies. The VMP

should add ress a ll of th ese concerns.The VMP serves the pur pose of documenting t he intent of

the validation program, and therefore needs to be pre-ap-

proved by the same departments that wi l l ul t imately be

responsible for reviewing a nd a pproving t he subsequent proto-

cols. At a minimum, t his includes Regulat ory Affairs, Qua lity,

and Engineering.

Opening a Dialogue with the FDAThere ar e a n umber of good reasons to create a VMP: t he FD As

expectat ion t ha t one be crea ted, determining r esource sched-

uling and loading, and defining the necessity to create or

amend corporate procedures. However, one function of the

VMP is often underutilized: serving as a vehicle to open up

dialogue between th e regiona l District Office of the FDA an d

the organizat ion. In i t iat ing a pre-submission m eeting w ith t he

FDA to review th e VMP w il l save t ime to ma rket by a ddressing

a ny concerns a bout th e valida tion philosophy or methodology

up front, w hen t he correction of those issues is not on a critical

pat h for time to mar ket. This a llows companies to work w ith

the FDA in an advisory versus an enforcement mode, which

w ill help ta ke some of the an xiety out of the valida tion process

and improves its chances of success. The FDAs Center forBiologics Evaluation and Research (CBER) has published a

document t hrough i ts Manua l of Sta ndar d Operat ing P roce-

dures and Pol icies tha t discusses this . I t suggests tha t a brief

description of the va lidation procedures including the va lida-

t ion master plan1 be submitted for review prior to the pre-

NDA (New D rug Applicat ion) meeting. Although t his proce-

dure w a s wr itten for B iologics, the benefits of such meetings

for Drug a nd Medical Device products is obvious, par ticularly

if there ar e unique processing steps and /or equipment tha t t he

a verage FD A compliance officer ma y not be familiar wit h.

Regulatory References to Validationand Planning

The FDA can determine prohibited acts a nd pena lize drug a nd

device ma nufacturers w ho market adulterat ed product .2 An

adulterated product is one whose quality characteristics can

not be satisfactorily assured due to nonconformity with cur-

rent G ood Manufacturing P ract ices (cGMP s)3. The d efinition

of adulterated product is s t raightforwa rd, but preventing i ts

occurrence ca n be complex. In essence, a Validat ion P rogram

ensures th a t syst ems, policies, and procedures exist to prevent

the ma nufacturing of adul terated products . I t s in the cG MPs

for Drugs (21CFR 210 & 211), Biologics (21CFR 600) and

Devices (21CF R 800) w here t he need for va lida tion is specified.

Drug Products

For drug products, Parts 210 and 211 of the cGMPs referloosely to maintaining appropriate val idat ion data . How-

ever, the pra ctice of validat ion is implied more strongly in

211.68 (a ): Automa tic, mecha nical, or electronic equipment or

other types of equipment, including computers, or related

Table A. Validation program.

Validation Program

Validation Master Plan (VMP) Documents Intent and Pathway

Qualification (IQ/OQ/PQ) Confirms Design Intent

Process Validation (PV) Assures Process Consistency

Final Reports (FR) Summarizes Test Results vs. Acceptance Criteria

Compliance Programs Ensures Continuing State of Validation

Table B. Typical VMP contents.

Typical VMP Contents

1. Introduction

2. Scope

3. Facility Description

4. Commissioning

5. Qualification

6. Process Validation

7. Computer System Validation

8. List of Required Protocols and Procedures

9. List of Required Standard Operating Procedures

10. Equipment and Utility System Descriptions

11. Computer System Description

12. Other cGMP Programs

13. References

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TheValidation Maste

Table C. List of required protocols and procedures.

Process Equipment/Other Systems

EQUIPMENT Comm. IQ OQ PQ PV

Reactor System Series 100

Centrifuge

Catch Tank

Solvent Storage and Distribution

Glass Lined Mix Tank and TCU

Utility Systems

UTILITY SYSTEM Comm. IQ OQ PQ PV

Fire Water System

Breathing Air System

Cold Glycol System

USP Water System

HVAC

LegendComm.: Commissioning

IQ: Installation QualificationOQ: Operational QualificationPQ: Performance QualificationPV: Process Validation

Not Applicable

systems that wi l l perform a functionsat isfactori ly , may be

used in the ma nufa cture, processing, packing, and h olding of

a drug product. The burden of proof lies with the manufac-

turer to show equipment will perform a fu nction satisfacto-

r i l y , an d th a t proof should ta ke the form of in-process testing

or alternately, Process Validation.

To clarify t he va lidation requirements implicit in th is regula-

tion, the Agency issued a Federal Register Notice proposing

changes to Parts 210 and 211.4 One change would offer this

definition: Vali dati on protocolmeans a written plan describing

the process t o be validat ed, including production equipment, a nd

how valida tion will be conducted .5Another proposed section

states: The manufacturers determination of equipment suit-

ability shall include testing to verify that the equipment is

capable of operating satisfactorily within the operating limits

required by the process.6In both of these cases, a w ell-crafted

VMP will show the Agency the pre-approved intent to comply

with the expectations of cGMP regulations.

BiologicsFor B iologics, P ar t 600 a ddresses unique considera tions as so-

ciat ed w ith biological products a nd blood components. B iologi-

cal-derived drug products must adhere to Parts 210 & 211.

Also, cGMP section 601.12 requires va lidat ion for chan ges to

an a pproved applica tion. Before distributing a product ma de

using a cha nge, an a pplican t sha l l demonstrate t hrough appro-

priate val idat ion the lack of adverse effect of the change on

the identity , strengt h, qua lity, purity, or potency of the prod-

u ct . 7 This requirement governs chan ges in product, pro-

duction process, quality controls, equipment, facilities, re-

sponsible personnel, or la beling .8 Whether the change is

major or minor, a VMP will provide the Agency the basic

components of the organizational validation philosophy and

intent ions to comply wit h a pplicable regulations.

Medical DevicesFor Medical Devices, 21 CF R 820 serves as t he cGMP require-

ments section. Section 820.75 deals with Process Validation

and sta tes that t he val idat ion act ivit ies and results , and

where appropriate the major equipment validated, shall be

documented.9This outlines the need for a va lidat ion progra m,

an d th e VMP can help comply with this requirement by docu-

menting w hich ma jor equipment systems w ill be validated.

Part 11All regulated industries are struggl ing to understand and

comply wit h th e requirements of 21CF R 11, wh ich a ddresses

Electronic Records and Electronic Signatures, and requires

Validat ion of systems to ensure a ccura cy, reliability, consis-

tent int ended performa nce, a nd th e ability to discern inva lid or

a ltered records.10

B ased on the num ber an d complexity of thecomputer syst ems utilized, a separa te Computer Syst em Va li-

dat ion Ma ster P lan ma y need to be wri t ten a nd referenced in

the VMP. H ere again, th is can serve as a vehicle for a pre-

execution meeting wit h th e FDA in order to gain guida nce.

These specific inst a nces do not explicitly deta il the requ ire-

ment for a Val idat ion Ma ster P lan; however, a properly crafted

VMP will document the pathway to compliance.

VMP ReferencesIncreasingly, the FDA is showing it agrees. Recently, the

Agency issued a Guidance for Industry document, meant to

reflect t he Agencys current th inking, th at explicitly calls out

for a VMP. In G uidance on Qua l ity S ystem Regulat ion In for-


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Table D. Example of an equipment and utility system description.

Section 10.0: Equipment and Utility System Descriptions

Nitrogen Distribution System

DescriptionNitrogen gas is distributed throughout the facility using a networkof carbon steel (from supply to inline filter) and stainless steel(from inline filter to use point) piping. Nitrogen gas is obtainedfrom an existing 400-psig nitrogen gas system located in thefacility.

A one-micron filter is utilized to filter high-pressure nitrogen tobe used in the Series 100 Reactor System for pressuring,purging, and for the agitator gland seal. Nitrogen line pressurefrom the header is reduced prior to use-point delivery. Low-pressure header branches service the tank farm and productionareas, and each branch will utilize a one-micron filter, as well asupstream and downstream pressure indicators to verify filtercartridge integrity.

Installation QualificationInstallation Qualification will be performed in accordance with theguidelines specified in SOP #95IQ001. All IQ data will bedocumented in an approved Installation Qualification protocol Protocol preparation, review, and approval will be scheduled tocoincide with the installation of the Nitrogen Distribution System.

Operational Qualification

Operational Qualification of the Nitrogen Distribution System willbe performed in accordance with the guidelines specified in SOP#95OQ001. Proposed OQ testing and the correspondingacceptance criteria are described below.

System Capacity Testing/Flow DeterminationUnder maximum use conditions (system design basis),nitrogen flow rate and system header pressure must remainacceptable.

Static Pressure TestingNitrogen pressure at usepoints must meet systemspecifications and end user requirements.

Performance QualificationPerformance Qualification of the Nitrogen Distribution System willbe preformed in accordance with the guidelines specified in SOP

#95PQ001. Proposed PQ testing and the correspondingacceptance criteria are described below.

Moisture/Dewpoint DeterminationThe measured dewpoint at selected usepoints must closelycorrespond to the dewpoint of the supply.

ParticulateParticulate measurements will be at or below predeterminedlevels.

Oxygen ConcentrationOxygen concentration at predetermined usepoints mustclosely correspond to the oxygen concentration of the supply.

ness, showing t he FDA tha t a ll systems have been examined for

product quality impact. To maximize the usefulness of commis-

sioning, the system should be tested within the anticipated

operat ing ra nge of the r espective OQ.

5. Qual if ica t ion

The selection criteria governing what equipment and utility

systems will undergo Qualification is discussed here. Indi-

vidua l definitions of IQ, OQ, an d P Q, ma y be included. Com-

pany policies, regulatory references, and published guide-lines used in this selection process should be addressed. This

discussion may include considerations such as product con-

ta cting su rfa ces, critical/non-critical instru menta tion, direct

mation for Various Pre-Market Submissions, a requirementof th e Quality Sy stem Ma nufa cturing Dossier is a copy of the

Validat ion Ma ster P lan or a descript ion of which manufa ctur-

ing processes have been or will be validated. A Validation

Master Pan is a convenient method of qual i ty planning for

process val idat ions required in the manufacturing of the

device ( 820.20(d)).11 C l e a r l y t he e xpe c t a t i o n o f t he

Agency is that organ izat ions have a va l idat ion stra tegy as part

of product and process development, and tra nslate th at s tra t-

egy into a plan t hat wi l l lead to an insta l lat ion compliant wi th

regulat ory requirements.

The Validation Master PlanListed below a re the hea dings for the ma jor sections of a VMP

followed by a description of the purpose and the suggestedcont ent - Tabl e B.

1. Int roduct ion

This section should include the company na me, locat ion, divi-

sion or subsidiary name (if applicable) and business sector

served. A short overview of the project provides th e reader wit h

the necessary ba ckground from a ma cro sta ndpoint. A cross-

reference to the relevant compa ny Qua lity Assuran ce P olicy is

appropriate here.

2. Scope

This section defines the breadth and reach of the validation

effort covered by the VMP. A brief description of the installa-

tion, whether single- or multi-product, and a breakdown of

insta lled equipment a s new or existing sh ould be included here.

3. Faci l i ty Descript ion

Whether th e project is a new building, extension, or r emodel-

ing of a curr ent building, the facility cha ra cteristics ar e listed

here. The number of floors, the inter-connectivity of process

and utility systems, isolation means, and the design product

an d personnel flow used to minimize cross-conta mina tion ar e

identified. Be su re to n ote an y r oom classification (cleanr oom

certification levels) and specialty surfaces and finishes inte-

gral to achieving the required product quality. Process Flow

Diagrams (PFDs) are useful here, depicting the anticipated

personnel , raw mat erial , process, and w ast e mat erial f low. Theemphas is here is on design considera tions to eliminat e cross-

conta minat ion of ma terial .

4. Commissioning

Document here the selection criteria governing w ha t equipment

and utility systems will undergo Commissioning. As Commis-

sioning is not par t of the Validat ion P rogram a nd is not regulat ed

by th e FD A, people often w onder wh y th ey should include this

section at all. The reason is th e FDA is just as interested in th e

ra tionale behind w hy one system is not validat ed while another

is. The VMP n eeds to answ er tha t q uestion, identifying support

utilities that do not need to be validated because they do not

directly affect product quality. It also demonstrates thorough-

address the selection crit eria governingwhat equipment and ut ilit y systems need toundergo Process Validat ion.

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TheValidation Maste

Wit h t he inclusion of some additional

info rmat ion the VM P can help serve as a

resource- and task-pl anning tool

and indirect systems,12 and downstream processing, among

others. A discussion of protocol and final r eport format s ma ybe included here, w ith either a reference to existing protocol

development procedures, or a description of the forma t to be

uti l ized. Final Reports ma y be generat ed as a t ta chments t o

the protocols themselves, or as separate documents.

6. Process Validation

This section addresses the selection criteria governing what

equipment a nd ut ility systems need to undergo Pr ocess Valida-

tion. Company policies, regulatory references, and published

guidelines utilized in t he selection process should be a ddressed.

One such criteria is if the results of a process cannot be fully

verified by subsequent inspection a nd test , the process sha ll be

va l ida ted . 13Also included is a discussion on th e appropria te

Cleaning Validations (CV) required to verify inter- and intra-

campaign cleaning methods. I f thi s is to be a fin ished pr oduct,

Packagin g and Steri li ty val id ati on needs to be addr essed.

7. Computer System Validat ion

A separate section should be devoted to the discussion of

Computer Validat ion, wh ether tha t is in the form of a P rogram-

mable Logic Controller (PLC) or a Distributed Control System

(DCS). Computer Validation criteria also should be discussed,

and whether the installed control system is to be 21 CFR 11

compliant, i.e., secure audit trails, authority checks, etc.

8. List of Required Protocols and Procedures

Include here a t abular representat ion of the equipment a ndutility systems, and the required protocols and procedures

associated w ith ea ch -Table C. This is t he essence of the VMP

becau se it defines the va lidat ion requ irements for th e project,

an d can be used to determine resource loa ding. This ta ble ca n

subsequently be used as a Deliverables List if the validat ion

effort is contra cted outside of the organ izat ion.

9. List of Required Standard Operating Procedures (SOPs)

This should take the form of a tabular representation of the

instal led equipment a nd ut i l i ty systems and the required SOP

associated w ith ea ch, similar t o the List of Required Protocols

and Procedures. This will help identify the level of SOP

generat ion n ecessary to complete valida tion a ctivities. These

will generally take the form of Operation, Maintenance, andCleaning SOPs.

10. Equipment and Ut ilit y System Descript ions

An overview of the par ticular sy stem sh ould be given, aligned

wit h th e Ba sis of Design documenta tion. Table D serves as a n

example of specific verbiage used in a typical VMP . A listing of

proposed Qua lificat ion t ests (IQ/OQ/P Q) should be ident ified

wit h a brief description of th e procedure a nd how the a ssoci-

ated Acceptance Criteria will be determined. As the VMP

should be developed early in th e plan ning sta ge, many sys tem

specifics w ill be in th e dra ft pha se an d subject t o cha nge. To

a void duplication of effort a nd un necessa ry r evisions, do not

a ssign n umer ic-specific Accepta nce Criter ia in t he VMP . Those

deta ils will be fully delineat ed in the r espective Qualificat ion

and Validation protocols that will follow. Keep in mind the

intent of the VMP a s a scope a nd guida nce document. Syst em-

specific acceptance criteria fall under the auspices of the

individual protocols.

11. Additional cGMP Programs

The VMP is mea nt to be a Valida tion Life Cycle document . It

should cover the activities and requirements from project

inception to testing completion a nd on th rough a program of

continuous monitoring and evaluation. Associated with this

effort ar e Qua lity Assura nce/Qua lity Contr ol procedur es meant

to support and update the validation effort. These programs

include, but a re not limited to:

11.1 Document/Change Control

A procedure mu st be in place to govern a nd ca pture documen-

ta tion creat ion, revision, an d control. This procedure w ill be

applicable to all validation documentation, and must desig-

na te the review a nd a pproval responsibilities of va rious func-

tional groups. Archival guidelines shall include duration of

record retention, and means of storage and retrieval.

11.2 Standard Operating Procedures

SOPs shal l exist to address such cGMP issues as faci l i ty

sanitation, waste collection and disposal, the use of suitable

rodenticides, insecticides, fungicides and fumigating agents,

an d bui lding ma intenance.

11.3 Calibration

A system shall exist detailing the methods, frequency, and

document a tion of the calibrat ion program including justifica-tion for a no calibration required status.

11.4 Preventative Maintenance

This syst em w ill be indexed to distinct equ ipment identifiers,

and outline the maintenance procedures required to ensure

proper syst em functionality. This procedure w ill ident ify th e

appropriate documentation and frequency requirements.

11.5 Revalidation

A crucia l part of the Validat ion program is determining w hen

to revalida te. This determina tion ma y be periodic, or triggered

by the replacement of cri t ical instrum ents. P art of the C han ge

Control program will be an assessment of the impact of any

proposed cha nge on the va lidated st at e of the a ffected equip-ment , a nd i f reval idat ion is r equired.

11.6 Operator Training

A program mu st exist to ensur e and document t ha t personnel

sha ll have t he appropriat e educat ion, tr ainin g, an d/or experi-

ence to perform their assigned functions. Personnel shall be

trained on good sanitation practices, as well as the use of

protective apparel to prevent product contamination.


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12.References

All company policies and procedures, as well a s a ny a pplicable

local , s tate and federal regulat ions, and industry standards

referenced should be listed.

Input to the VMPA certa in minimu m level of documenta tion needs t o be devel-

oped in order to produce a VMP. An equipment list, which

provides basic specificat ions such as size/capa city, inst rum en-

ta tion a nd controls, design/operat ing limits, a nd capa bilitiesneeds to be available. Additional documentation such as a

Design B asis is importa nt t o del ineate how equipment a nd

utility syst ems should perform, independently a nd in concert,

to produce the product. For Biologics and Pharmaceuticals,

general ly a set of prel iminary Piping and Instrumentat ion

Dia gra ms (P&ID s) helps define system bounda ries. For Medi-

cal Devices, the Ma nufacturing Flow Dia grams required in the

Ma nufa cturing Dossier section of the Pre-Ma rket Su bmission

also may provide system boundary information.

Approval of the VMP pr ior t o the generat ion of the a ssoci-

at ed protocols is a s importa nt a s a pproval of protocols prior t o

da ta collection. J ust as protocols require QA approval prior to

execution, the VMP requires QA approval prior to protocol

generat ion. The VMP should be under r evision control, as it

documents corporate approval of the scope and intent of the

validation program, and will require QA approval. Any Basis

of Design or validation philosophy changes should be pre-

approved in the VMP prior to the generation of the affected

protocols. The VMP needs to be updated to document major

project scope changes such as the addition or deletion of

equipment, and project completion (i.e., release to produc-

tion). This provides a clean au dit t ra il of pre-approved intent

versus execution.

ConclusionIn its simplest form, the VMP is meant to document th e major

equipment an d utility systems associa ted with t he productionprocess, assess the impact on the quality of the resulting

product, an d determine the valida tion requirements. With th e

inclusion of some a dditional informa tion; however, th e VMP

can help serve as a resource- and task-planning tool. For

insta nce, a Deliverables List ca n be developed from the List of

P rotocols, wh ich can be used to ga uge the ma n-hour require-

ments of the job, for either internal budgeting or comparing

outside contractor quotes. The Additional cGMP Programs

section can isolate the need for policies or procedures to be

created a nd/or upda ted.

The creat ion of a VMP a t t he beginning of the project serves

ma ny purposes: to identify t he timing a nd level of a nticipated

resource needs, to document t he corpora tions va lidat ion ph i-

losophy a nd individua l elements, a nd t o show t he FDA the pre-approved intent to bring on a new product line in full compli-

ance. I t is wel l worth the extra t ime spent to wri te this

document at project inception, and to get early regulatory

feedba ck via a pre-submission meeting w ith th e FDA, than to

answer Agency questions during the approval cycle and pay

with a delayed product laun ch date.

References1. U.S . Food and Drug Adminis t ra t ion, Manual of S tanda rd

Operat ing Pr ocedures and P olicies, Communicat ion, SOP P

8101.1, Version 1, Effectivit y da te Febr ua ry 11, 1999.

2. Federal Food, Drug an d Cosmetic Act , Cha pter III , Sec-

tions 301, 303, 304, as am ended by t he F DA Modernizat ion

Act of 1997.

3. Federal Food, Drug an d Cosmetic Act , Chapter V, Sect ion

501 (a)(2)(B ), a s a mend ed by t he FD A Modern iza tion Act of

1997.

4 . U.S . Food and Drug Adminis t ra t ion, 21 CFR par ts 210 &

211, Pr oposed Rule, Federa l Register, Fr iday Ma y 3 1996

D ocket N o. 95N-0362.


211, Pr oposed Rule, Federa l Register, Fr iday Ma y 3, 1996

Docket No. 95N-0362, page 20113, proposed 210.3 (b)

(23).


211, Pr oposed Rule, Federa l Register, Fr iday Ma y 3, 1996

D ocket N o. 95N-0362, pa ge 20115, proposed 211.220 (c).

7. U.S. F ood and Drug Administra t ion, 21 CFR 601.12 (a) ,April 1, 2000.

8. I B I D

9. U.S. F ood and Drug Administra t ion, 21 CFR 820.75 (a) ,

April 1, 2000.

10. U .S. Food a nd Dr ug Administra tion, 21 CFR 11.10 (a),

April 1, 2000.

11. U.S. F ood and D rug Administrat ion, G uidance for Indus-

try a nd/or for FD A St aff: G uida nce on Quality Syst em

Regulat ion I nformation for Var ious P reMarket S ubmis-

sions, Dra ft G uidance-Not for I mplementat ion, Dr aft re-

leas ed for comm ent on August 3, 1999, Section 19. Design

Hist ory File (DH F).12. I S PE Ba s el ine Ph arm aceutical Engineering Guide: P ha r-

maceutical Engineering Guides for New and Renovated

Facilities; Volume 3, Sterile Manufacturing Facilities,

First Edit ion, J an ua ry 1999, pages 119-120.

13. U .S. Food and D rug Administra tion, 21 CFR 820.75 (a),

April 1, 2000.

About the AuthorBrian W. Saxtonis a Regiona l Complian ce Ma na ger for Int e-

gra ted P roject S ervices in B urlington, MA. He is responsible for

client-based compliance programs including cGMP program

development, Validat ion Ma ster P lann ing, Pr otocol generation

a nd execution, an d Fina l Reporting. H e has been involved indeveloping a nd executing va lidation program s for th e past 12

years for various regulated industries. He has a BS in chemical

engineering from Manh at ta n College, B ronx, New York, and a n

MB A from Boston Un iversity, Boston, MA.

Int egrat ed P roject S ervices, 35 Corpora te Dr ive, 4th floor,

Burlington, MA 01803. [email protected].

Reprinted from Phar maceuti cal En gineeri ng,Ma y/J un e 2001,by The R eprin t D ept. 800-259-0470