Good Documentation Practices

3
OBJECTIVES

 DOCUMENTS IMPORTANCE

 PURPOSE OF DOCUMENTS

 WARRNING LETTERS REVIEW

 DOCUMENTATION REQUIREMENTS

 RECORDING PRACTICES

 TYPE OF DOCUMENTS
 4
Why are documents so important?

EU, PIC/s GMP chapter 4, WHO GMP chapter 15:

Good documentation is an essential part of the QA system and key to operation in

compliance with GMP requirements.

.‫ می باشد‬GMP ‫ کلید انطباق فرایند ها با الزامات‬J‫ب بخش اساسی سیستم تضمین کیفیت و‬J‫مستندات و مستندسازي خو‬
 5
Why are documents so important?

21CFR 211.180(e):

Written records…shall be maintained so that data therein can be used for evaluating…the quality standards
of each drug product…“

.‫یی استفاده نمود‬J‫ل دارو‬J‫ کیفی محصو‬J‫ند تا بتوان از آنها جهت بررسی و ارزیابی با استاندارهای‬J‫کلیه سوابق باید نگهداری شو‬

Documents provides the route for auditors to assess the overall quality of operations and the final product.
.‫ بازرسین فراهم می کند‬J‫ محصول را برای‬J‫مستندات امکان ارزیابی همه جانبه کیفیت انجام فرایندها و‬
 ‫‪6‬‬

‫‪Purpose of documentation‬‬

‫‪‬‬ ‫‪To define specifications and procedures for all materials and methods of manufacture and‬‬
‫‪control‬‬
‫تعیین و کتبی کردن مشخصات و‪ J‬دستو‪J‬رالعمل های ساخت و تولید براي تمامی مواد و محصو‪J‬الت‬

‫‪‬‬ ‫‪To ensures all personnel concerned with manufacture, know what to do and when to do it‬‬
‫اطمینان از اینکه پرسنل تولید بدانند چه می کنند؟ و چه زمان باید آن را انجام دهند؟ (مستندسازي و‪J‬اضح از اشتباهات ناشی از ارتباطات شفاهی جلو‪J‬گیری می کند‪).‬‬

‫‪‬‬ ‫‪To ensure that authorized persons have all information necessary for release of product‬‬
‫اطمینان از اینکه آیا مسئول فنی و مدیر آزمایشگاه کلیه اطالعات الزم براي آزادسازي یک بچ محصول را براي فروش در اختیار دارند؟‬
 7

Purpose of documentation

 To ensures documented evidence, traceability, provide records and audit trail for investigation
)‫ یا تحقیق (سیستم ثبت یعنی اثبات انجام فعلی در گذشته با نشان دادن مستندات‬J‫اطمینان از وجود سوابق قابل پیگیری برای بازرسی و‬

 To Ensures the availability of data for needed for validation, review and statistical analysis
‫ بایگانی براي یک مانور یا آزمایش بازرسی و امکان تفحص از مستندات‬J‫موجود بودن سوابق و‬
 8
Purpose of documentation

EU, PIC/s GMP chapter 4:

The main objective of the system of documentation utilised must be to establish, control, monitor and
record all activities which directly or indirectly impact on all aspects of the quality of medicinal products.

There are two primary types of documentation used to manage and record GMP compliance: instructions
(directions, requirements) and records/reports.

‫ه های کیفی‬J‫تقیم بر تمام جنب‬J‫ر مس‬J‫ا عی‬J‫تفیم ی‬J‫ه مس‬J‫ت ک‬J‫ی اس‬J‫ت های‬J‫ه فعالی‬J‫وابق کلی‬J‫ت س‬J‫ش و ثب‬J‫ پای‬،‫یستم کنترل‬J‫ک س‬J‫تندسازی بوجود آوردن ی‬J‫یستم مس‬J‫لی از س‬J‫هدف اص‬
.‫محصول دارویی تاثیر می گذارند‬

.‫گزارشات می باشد‬/‫ شامل دستورالعمل ها و سوابق‬GMP ‫ ثبت و و ایجاد سابقه برای اثبات انطباق با الزامات‬،‫دو دسته اصلی مستندات برای مدیریت‬
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Review of warning letters (FDA form 483)
 The Top 10 Pharmaceutical Deficiencies Cited by FDA in 2015
 
Short Description Long Description Frequency
Procedures not  in writing, fully The responsibilities and procedures are not [in writing] [fully followed].  160
1 followed

Scientifically sound laboratory Laboratory controls do not include the establishment of scientifically sound and 130
controls appropriate [specifications] [standards] [sampling plans] [test procedures]
2 designed to assure that [components] [drug product containers] [closures] [in-
process materials

Investigations of discrepancies, There is a failure to thoroughly review [any unexplained discrepancy] [the failure 124
failures of a batch or any of its components to meet any of its specifications] whether or
3 not the batch has been already distributed.  Specifically

Procedures for sterile drug Procedures designed to prevent microbiological contamination of drug products 104
products purporting to be sterile are not [established] [written] [followed].  Specifically
4

Absence of Written Procedures There are no written procedures for production and process controls designed to 95
assure that the drug products have the identity, strength, quality, and purity they
5 purport or are represented to possess.  Specifically
 
Short Description Long Description Frequency
Environmental Monitoring System Aseptic processing areas are deficient regarding the system for monitoring
6 environmental conditions.  Specifically, 83

Testing and release for distribution Testing and release of drug product for distribution do not include appropriate
laboratory determination of satisfactory conformance to the [final
7 specifications] [identity and strength of each active ingredient] prior to 80
release.  Specifically,

Control procedures to monitor and Control procedures are not established which [monitor the output] [validate
validate performance the performance] of those manufacturing processes that may be responsible for
causing variability in the characteristics of in-process material and the drug
8 69
product.

Cleaning / Sanitizing / Maintenance Equipment and utensils are not [cleaned] [maintained] [sanitized] at
appropriate intervals to  prevent [malfunctions] [contamination] that would
9 alter the safety, identity, strength, quality or purity of the drug product.  68
Specifically,

Calibration/Inspection/Checking not Routine [calibration] [inspection] [checking] of  [automatic] [mechanical]

done [electronic] equipment is not performed according to a written program
10 designed to assure proper performance.  Specifically, 64
 12
Review of warning letters

While the definition of GDPs may be one that is universally understood, the practice itself can often be
confusing.

Most FDA violations involve one of the following:

 Not having procedures in a regulated area that conform to FDA regulations

 Having procedures that conform to FDA regulations, but not following them
 Having procedures that conform to FDA regulations and following them, but not having adequate
documentation to show that you’re following them.
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Dr Reddy`s laboratories, Nov 2015

 Failure to record activities at the time they are performed.

Your employees did not complete batch production and control records immediately after activities were
performed. When QA reviewers noticed missing entries in the batch records, they made a list of all the
missing items on separate, uncontrolled pieces of paper that were provided to the production manager. Data
were later entered into cGMP documents after operations had already ended as though they had been
entered at the time of the operation.
 14
Dr Reddy`s laboratories, Nov 2015

 Failure to maintain complete data derived from all laboratory tests conducted to ensure compliance with
established specifications and standards.

Your laboratory records did not contain all raw data generated during each test for API batches
manufactured at your firm. The investigator found that batch samples were routinely re-tested following
failing or atypical results until acceptable results were obtained, and that failing or atypical results were
not investigated or included in the official laboratory control records.
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Warning letter -September 2015

 1.    Failure to document production and analytical testing activities at the time they are performed.

The results and other entries in the production records were not entered while batches were in production.
 For example:

a) The start and stop times were not recorded or signed in the batch record contemporaneously.

b) Water testing records for sampling point (b) on March 19, 2014, were incomplete.
 16
Warning letter -September 2015

 2.    Failure to prevent unauthorized access or changes to data and to provide adequate controls  to

prevent omission of data.

 Your laboratory systems lacked access controls to prevent raw data from being deleted or altered.  For
example: 

a) You had no unique usernames, passwords, or user access levels for analysts. They could delete or alter
chromatograms, methods, integration parameters. You used data generated by these unprotected and
uncontrolled systems to evaluate API quality. 

b) Multiple instruments had no audit trail functions to record data changes.  

 17
Mark Bioscience, September 2014

 “Our inspection revealed ‘unofficial’ visual inspection records, signed by production personnel, with
data that is different from the official batch records re-viewed by your firm’s quality unit,” the letter
stated. many of the cases reviewed, the unofficial records showed significantly more quality defects
than the official batch records.”
 The top most frequently deviations (PIC/s)
 Documentation—manufacturing (24)

 Design and maintenance of premises (22)

 Documentation—quality systems (elements / procedures) (20)

 Personnel issues—training (19)

 Design and maintenance of equipment (18)

 Cleaning validation (14)

 Process validation (14)

 Product quality review (14)

 Supplier and contractor audit (13)

 Calibration of measuring and test equipment(12)

The top most severe deviations 19
 20
Type of documents

 Standard Operating Procedure (SOPs)………………………………………………………‫ک‬J‫ار را‬JJJ‫ستاندارد ک‬J‫)روشهایا‬

 Batch Manufacturing/Production Record (BMR/BPR)
 Standard Testing Procedure (STPs)
 Specifications ……………………………………………………………………………………………………...‫مشخصات‬
 Records……………………………………………………………………………………………………............. ‫بق‬J‫وا‬JJ‫س‬
 Labels ………………………………………………………………………………………………………………. ‫رچسب‬JJJ‫ب‬
 Logbooks ……………………………………………………………………………………………………......... ‫بت‬JJJ‫دفتر ث‬
 Master formula
 Other documents (SMF, Technical agreement Drawing, Flowcharts, Pictures, …)
 21
General requirements

1- Preparation
‫تهیه و تدوین مستندات‬

2- Control and distribution

‫کنترل و توزیع مستندات‬

3- Data entries
‫ثبت داده ها‬

4- Retention
‫نگهداری مستندات‬
 ‫‪22‬‬
‫‪1- Preparation‬‬

‫‪‬‬ ‫‪To be comply with marketing authorization‬‬

‫مستندات باید با قسمتهاي ذیربط پروانه بهره برداري و‪ J‬پروانه ساخت منطبق باشد‪.‬‬

‫‪‬‬ ‫‪To be designed, prepared, reviewed and distributed with care‬‬

‫اسناد باید بدقت طراحی‪ ،‬تهیه‪ ،‬بررسی و توزیع شوند‪ .‬طراحی مستندات و‪ J‬نحوه استفاده از آنها بستگی به سازنده دارد‪.‬‬

‫‪‬‬ ‫‪To be approved, signed, and dated by the appropriate competent and authorized persons. The effective‬‬

‫‪date should be defined‬‬

‫باید مستندات توسط اشخاص دارای صالحیت تائید‪ ،‬امضا‪ ،‬و تاریخ زده شود‪ .‬تاریخ اجرای‪ J‬هر سند باید ذکر شود‬
 23
1- Preparation Cont.

 To have clear/unambiguous contents and be identifiable. (e.g. title, nature, and purpose)
‫محتویات مستندات باید واضح باشند و هر سند کد شناسایی اختصاصی داشته باشد‬.

 Instructions style to be in the imperative (Mix, Wash, Do, Add, etc.)

‫سبک نگارش دستورالعمل ها باید به صورت جمالت امری باشد‬.

 Short and simple sentences preferred to long, florid sentences

‫بیان جمالت کوتاه و ساده بهتر از جمالت طوالنی و پیچیده‬

 Sufficient space must be provided for such entries

.‫فضای کافی برای ثبت اطالعات داشته باشد‬

 Not be handwritten ‫اشند‬JJJ‫ویسب‬JJ‫بایستیدستن‬JJ‫تن‬J‫مستندا‬

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2- Control and distribution

 Documents within the Quality Management System should be regularly reviewed and kept up-to-date.
..‫ند‬J‫ن سیستم مدیریت کیفیت تطور منظم و دوره ای مرور و بررسی و بروز رسانی شو‬J‫مستندات باید درو‬

 QMS should be operated to prevent inadvertent use of superseded documents.

.‫باید سیستم کنترل مستندات به گونه اي عمل کند تا از استفاده غیر عمد از اسناد جایگزین شده (قبلی یا تاریخ گذشته شده) جلوگیري و اجتناب کند‬

 Documents should be available at point of use

 25
2- Control and distribution

 Unauthorized photocopying of original documents should be actively discouraged. (MASTER COPY,

Operational Copy stamp)
.‫گیری شود‬J‫از تهیه رونوشت های غیر مجاز باید جلو‬

 Clear and readable – including copies made

.‫مستندات کپی شده باید واضح و خوانا باشند‬

 No errors if master documents are copied for working documents

.‫نه اي باشد که اشتباه ي در کپی بوجود آید‬J‫کپی کردن مستندات کاري از سند اصلی نباید به گو‬
 26
3- Data entry

 Shall be done at the time of action not be made prospectively or retrospectively.

.‫ثبت و ایجاد سابقه باید در زمان انجام یک فعالیت انجام شود‬

 Use indelible blue ink. ‫ود‬JJ‫ ش‬J‫ستفاده‬J‫شدنیا‬JJ‫اکن‬JJJ‫بیپ‬J‫ودکار آ‬J‫از خ‬

 To be clear, readable and indelible ‫شدنی‬JJ‫اکن‬JJJ‫ پ‬J‫نا و‬J‫وا‬J‫ خ‬،‫ضح‬J‫وا‬

0 6
U V
S 5
(102 ≠ 1.2) (65 ≠ 65) (9 ≠ 9) (4 ≠ 9) 1 7
3 8
B 8
 27
3- Data entry – cont.

 Attach printouts, if any. Printouts to be signed and dated.

.‫یخ زده شود‬J‫ پیوست ها باید امضاء و تار‬.‫پرینت ها بایستی پیوست ثبت نامه ها گردند‬

 To avoid the use of thermal paper for printing the documents. In case of use, the photocopy to be
attached to the original document.
.‫تی برای چاپ اسناد مجاز نیست مگر عکس سند اصلی ضمیمه گردد‬J‫استفاده از کاغذهای حرار‬

 No spaces for handwritten entries should be left blank. If unused, they are crossed out or “NA“ for not
applicable (or similar text) entered
.‫ناد نباید خالی رها شود و باید با عبارت های کاربرد ندارد یا کشیدن خط تیره تکمیل شود‬J‫مت های دستنویس اس‬J‫هیچ یک از قس‬
 28
3- Data entry – cont.

 Entries for checks shall be mentioned as complies if within spec limits/ satisfactory in case for
observations. Do not mention as okay / good.
.‫قسمتهای نیازمند کنترل و یا مشاهده بایستی با عبارت «تطابق دارد» یا «مطلوب» تکمیل شوند‬

 Don’t Use of ditto marks (“) ‫یست‬JJ‫یضا " مجاز ن‬J‫عالمت‬

‫ا‬ ‫ از‬J‫ستفاده‬J‫ا‬

 Data should be congruent with limit ‫اشد‬JJJ‫نب‬J‫ ها همخوا‬J‫ا محدوده‬JJJ‫ایستب‬JJJ‫تایج ب‬JJ‫ن‬.

5.96
Limit: 5.50-6.00 Result: 6.0 6.04
 29
3- Data entry – cont.


Use defined format for date and time 14:35, 1394/12/10, 2016-08-07 (YYY-MM-DD)
.‫قالب استاندارد برای ثبت تاریخ و ساعت باید مطابق قالب زیر باشد‬

 For electronic data, only authorized persons should be able to enter or modify data in the computer, access should
be restricted by passwords.

.‫د‬J‫ بایستی سطح دسترسی و رمز عبور برای افراد تعریف شو‬.‫اصالح نمایند‬/‫ارد‬J‫انند داده های الکترونیک را و‬J‫تنها افراد دارای ضالحیت می تو‬
 30
4- Retention

 To define which record is related to each manufacturing activity and where this record is located

.‫تعریف ارتباط سوابق به فعالیت های تولید و محل نگهداری آنها باید تعریف شود‬

 Secure controls must be in place to ensure the integrity of the record throughout the retention period and validated where
appropriate.

.‫بایستی کنترل های ایمن در محل نگهداری فراهم شود تا از دست نخوردن اسناد در طول نگهداری اطمینان حاصل شود‬

 Batch documentation must be kept for one year after expiry of the batch to which it relates or at least five years after
certification of the batch by the Authorized Person, whichever is the longer

.‫ نگهداری شوند‬-‫اسناد و سوابق بچ باید تا یک سال بعد از انقضاء بچ یا پنج سال بعد از گواهی آنالیز – هرکدام طوالنی تر باشد‬
 31
4- Retention cont.

 For investigational medicinal products, the batch documentation must be kept for at least five years after the
completion or formal discontinuation of the last clinical trial in which the batch was used.
‫ سال بعد از تکمیل آخرین مطالعه بالینی یا بعد از خاتمه رسمی آخرین مطالعه بالینی از بچ استفاده شده‬5 ‫مستندات بچ محصوالت مطالعات بالینی باید‬
.‫نگهداری شوند‬
 For other types of documentation, the retention period will depend on the business activity which the documentation
supports.
.‫دوره نگهداری سایر مستندات به فعالیت مرتبط با آن سند ارتباط دارد‬
 Critical documentation, including raw data (for example relating to validation or stability), which supports
information in the Marketing Authorization should be retained whilst the authorization remains in force.
.‫معتبرسازی که پستیبان اطالعات پروانه تولید هستند باید تا زمان اعتبار پروانه نگهداری شوند‬/‫اسناد مهم همانند اطالعات پایداری‬
 32
4- Retention cont.

 It may be considered acceptable to retire certain documentation (e.g. raw data supporting validation reports or
stability reports) where the data has been superseded by a full set of new data.
.‫پایداری هستند به شرط جایگزینی با اسناد جدید قابل قبول است‬/‫کنار گذاشتن برخی اطالعات که پستیبان گزارش های معتبرسازی‬
 33
Common documentation errors appeared in FDA warning letters

 Documentation not contemporaneous

 Use of ditto marks

 Failure to use ink as specified by procedure

 Incorrect ink used for entries causing illegible data when a substance was spilled

 Logbook corrections failed to identify person who made the changes

 Obscured original data

 34
Common documentation errors appeared in FDA warning letters-
cont.

 Use of pencil
 Inaccurate records
 Sample sequence table and audit trail not documented (to draw on the commonly used phrase: "if it is not
documented, it didn't happen")
 Handwritten changes not dated
 Write-overs, multiple line-through, and use of "white-out" or other masking device
 35
Error Correction

Correction of documentation errors should include:

 Draw a single line through the error, so that the original records are always visible
.‫ بطوریکه داده اول قابل مشاهده باشد‬،‫ خط بروی داده غلط بکشید‬J‫یک‬

 Make the correction next to the error,

.‫اصالح الزم را در کنار داده اشتباه ثبت کنید‬

 Write an explanation for the error,

.‫توضیح الزم برای اشتباه صورت گرفته را بنویسید‬

 Sign and date the correction.

.‫اصالح صورت گرفته را با درج تاریخ و امضاء تایید نمایید‬
 36
Example of correction

 Correction performed immediately after the error was made.

Weight 56.5 mg Masoud 1394/12/21

65.5 mg Masoud
1394/12/21
 Correction performed the day after the error was made.

Weight 56.5 mg Masoud 1394/12/21

65.5 mg Transcription error, check the printing

weight

Masoud 1394/12/22
 37
Example of date correction

 Date Correction

1394/12/10 12 Masoud NOT CORRECT!

1394/12/10 1394/12/12 Masoud CORRECT

 38
Type of documents

 Standard Operating Procedure (SOPs)………………………………………………………‫ک‬J‫ار را‬JJJ‫ستاندارد ک‬J‫)روشهایا‬

 Batch Manufacturing/Production Record (BMR/BPR)
 Standard Testing Procedure (STPs)
 Specifications ……………………………………………………………………………………………………...‫مشخصات‬
 Records……………………………………………………………………………………………………............. ‫بق‬J‫وا‬JJ‫س‬
 Labels ………………………………………………………………………………………………………………. ‫رچسب‬JJJ‫ب‬
 Logbooks ……………………………………………………………………………………………………......... ‫بت‬JJJ‫دفتر ث‬
 Master formula
 Other documents (SMF, Technical agreement Drawing, Flowcharts, Pictures, …)
 39
Standard Operating Procedure (SOP)

 Title; To be brief and direct ‫ا محتوا‬JJJ‫ ب‬J‫ و ارتباط مستقیم‬J‫ خالصه‬:‫عنوا_ن‬

Operation and cleaning of vial filling machine,

Sampling of raw material,

 Purpose: to expand the procedure further which was not possible in the title
‫ توضیح بیشتر روش کار‬:‫هدف‬

To provide a procedure for raw materials and packing materials sampling in order to get a
representative sample of the whole lot for analysis.
 40
Standard Operating Procedure

 Scope: Very important section as it informs the person what a particular SOP does and
does not apply to.

For example:
Measurement of absorbance of protein using a colorimetric assay at 590 nm for in process control. (not the
spectrophotometer in the QC laboratory)

This SOP is applicable for estimation of binding potency of Drug Substance and Drug product of AltebrelTM to
TNFα for release and stability testing in quality control department of AryoGen Pharmed.
 41
Standard Operating Procedure

 Responsibility: Who is responsible for performing and supervising the SOP.

 Safety: Specifies all requirement for safe operation including operator,

equipment, environment

 Equipment: Specifies all required equipment with ID number, required number if

applicable

 Material: Specifies all required material with ID number, required amount

 42
Standard Operating Procedure

 Preliminary operation:
is optional and may or may not be relevant to the SOP such as:

A check list to ensure all the relevant materials required for the procedure are assembled prior to starting

The sanitization of biosafety cabinet before starting a procedure.

Preparation of fresh solution

 43
Standard Operating Procedure

 Abbreviation:Specifies all mentioned abbreviation in the all section

 Reference: Specifies all required and mentioned reference including the other SOPs and
records
 44
Standard Operating Procedure

 Procedure:

Simple and short J‫وتاه‬JJJ‫ و ک‬J‫اده‬JJ‫جمالتس‬

Clear and instructive ‫ضح و دستوری‬J‫توا‬J‫عبارا‬

A step by step in an orderly / sequential manner ‫ار‬JJJ‫رتیبک‬JJJ‫ ت‬J‫ه‬JJJ‫ و ب‬J‫ مرحله‬J‫ه‬JJJ‫ ب‬J‫وضیح مرحله‬JJJ‫ت‬

Accurate, Informative J‫موزشدهنده‬J‫ آ‬J‫یاندقیقو‬JJJ‫ب‬

Using picture, tables, and simple diagrams and an example may speak a 1,000 words
Confirm compliance with cGMP GMP‫صول‬J‫ا ا‬JJJ‫مطابقتب‬

Critical Parameter
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In process control ‫لید‬J‫و‬JJJ‫نترلهایحینت‬JJJ‫ک‬

Storage condition (container, temperature, time, caution) )J‫زم‬J‫حتیاط هایال‬J‫ ا‬J‫ زمانو‬،‫(ظرف دما‬
، ‫داری‬J‫گه‬JJ‫یط ن‬J‫را‬JJ‫ش‬
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Writing style

SOP is directive documents which describe a process with sufficient detail so that someone with limited experience or
knowledge, but with a basic understanding, can successfully reproduce the procedure when unsupervised.

Don`ts Do`s

Good ‫خوب‬ Three time/till to be clear ‫تـــ شفـاف شـدن‬

‫ ا‬/‫بــــ‬
‫ار‬ ‫سـهـ‬

Enough ‫افی‬
‫کـــ‬ X to y minutes/hours ‫ ساــعت‬/ ‫دـقیقهـ‬

Sufficient ‫افی‬
‫کـــ‬ X time

If required ‫اشد‬
‫اگر الــزم بــــ‬ When … it is required

According to procedure Based on SOP XX-YY-001

‫مطابق دستورالعمل‬
 47
Batch Manufacturing/Production Record (BMR/BPR)

 A Batch Processing Record should contain the following information:

‫ثبت نامه های تولید بایستی شامل موارد زیر باشد‬

a) The name and batch number of the product

‫نام و شماره بچ محصول‬

b) Dates and times of commencement, of significant intermediate stages and of completion of production
‫ فرایند های حد واسط و محصول نهایی‬،‫تاریخ و زمان شروع فرایند اصلی‬

c) Identification (initials) of the operator(s) who performed each significant step of the process and, where
appropriate, the name of any person who checked these operations;
‫ابتدای نام کاربرها انجام دهنده فرایندهای مهم و در موارد الزم نام فرد کنترل کننده‬
 48
BMRs/BPRs

d) The batch number and/or analytical control number as well as the quantities of each starting material actually
weighed (including the batch number and amount of any recovered or reprocessed material added)
‫ مقادیر واقعی مواد اولیه‬،‫کنترل حین تولید‬/‫شماره بچ‬

e) Any relevant processing operation or event and major equipment used;

‫توضیح تمام فرایند های اجرایی و تجهیزات اصلی‬

f) A record of the in-process controls and the initials of the person(s) carrying them out, and the results obtained;
‫ نتایج و ابتدای نام افراد‬،‫ حین تولید‬J‫ثبت کنترل های‬

g) The product yield obtained at different and pertinent stages of manufacture;

‫میزان بازده در مراحل مختلف و مهم تولید‬
 49
BMRs/BPRs

h) Notes on special problems including details, with signed authorization for any deviation from the Manufacturing
Formula and Processing Instructions;
‫ثبت مغایرت ها با جزییات و امضا تایید آن‬

i) Approval by the person responsible for the processing operations.

‫تایید شخص مسئول فرایند‬
 50
Log books

 Logbooks should be kept for major or critical analytical testing, production equipment,
and areas where product has been processed.

 They should be used to record in chronological order, as appropriate, any use of the area,
equipment/method, calibrations, maintenance, cleaning or repair operations, including the
dates and identity of people who carried these operations out.
 Cleaning process should be checked by witness.
 51
Labels

 What must be labeled?

Containers, Equipment, Premises

 Label information

Clear, company format, indicating the status

 52
Reference standard label

 Label to be include:
• Name
• Potency or concentration
• Date of manufacture
• Expiry date
• Date the closure is first opened
• Storage condition
• Control number