DEVELOPMENT OFDEVELOPMENT OFPHARMACEUTICALDOCUMENTATIONPHARMACEUTICALDOCUMENTATION

Document is a written report or record that provides information.

Documentation is a method of preparing a written material, which describes the process in terms of specifications ,instructions etc.

Document is a piece of written, printed or electronic matter that provides information or evidence.

A Good Documentation is essential part of QA system .

Documentation is an important aspect in pharmaceutical industry irrespective of the fact the manufacturing plant is involved in production of dosage form (or) active ingredient.

Importance of documentationImportance of documentation It provides the working details necessary for manufacturing,

packaging, quality control.

Reduce the risk of mistakes inherent in verbal communication.

They help in decreasing the batch to batch variation so that quality of product is kept with in the limit of acceptability.

Documentation and records are essentials for obtaining ACCREDIATION ,certification of ISO, and approval by Federal bodies.

Aims of documentationAims of documentation

To define the specifications for all materials To define the methods of manufacture and control To instruct the personnel To provide information during investigation To helps in inspection or auditing by Regulatory

authorities.

WHY DOCUMENTATION:

•There is a saying in the pharmaceutical industry: 'if it hasn't been documented, then it hasn't happened!' •Good documentation practice constitutes an essential part of the QA system. •Documentation system must be proactive vehicle of communication.

“YOUR DOCUMENTATION IS AN ADVERTISEMENT FOR YOUR WORKˮ.

To design an effective & efficient documentation

• Identify the important characteristics of processing event.

•The document directing the manufacturing event fulfills current regulatory commitments to the agency; it is appropriately written, reviewed and approved.

•The directive document is appropriate for the task to be performed.

•The data is authentic, accurate, complete, legible, accessible.

•The data collected fulfills expectations (specifications) and is retrievable for review or audit.

“All documentation should be legible, clean, readily identifiable, retrievable and maintained in facilities that provide a suitable environment to minimize deterioration or damage and to prevent loss”.

TYPES OF DOCUMENTS

Commitment Documents : Relationship between industry and the regulatory authorities.

EX: New Drug Applications (NDAs), Drug Master Files (DMFs) etc.

Directive Documents : Relationship between the Management and Employees.

EX: Specifications, STPs, Standard Operating Procedures (SOPs), Medicinal Product Records (MPRs) etc.

Record Documents : Relationship between the Employees and the Work they perform.

EX: Protocols, Batch Production Records (BPRs), Log Books, Calibration Records etc.

Commitment Documents

•These present corporate goals, expectations and standard of practice.

• It describes what to do.

• Consensus of purpose, direction and authorization for projects.

• It organizes the work in a manner that assures efficient and effective work flow.

• Commitments documents can also be written to establish internal commitments. Written to lead and guide the work and workers.

•These documents such as master plans; organize and prioritize the work in a manner that supports good business practice as well as regulatory compliance.

•To be used as active documents that are consulted and followed routinely.

•Content must be consistent and rigorous in order to lead and guide the work and the workers.

•Must describe the work as it will be done.

•Deviations from regulatory submissions can have signification impact on product quality.

•Any deviation must be documented and managed.

• New Drug Applications (NDAs):

The New Drug Application (NDA) is the vehicle in the United States through which drug

sponsors formally propose that the FDA approve a new pharmaceutical for sale and marketing.

The goals of the NDA are to provide enough information to permit FDA reviewers to establish the following:

•Is the drug safe and effective in its proposed use(s) when used as directed, and do the benefits of the drug outweigh the risks?

•Is the drug’s proposed labeling (package insert) appropriate, and what should it contain?

•Are the methods used in manufacturing (Good Manufacturing Practice, GMP) the drug and the controls used to maintain the drug’s quality adequate to preserve the drug’s identity, strength, quality, and purity?

•Drug Master Files (DMFs):

Drug Master File (DMF) is a document containing complete information on an Active

Pharmaceutical Ingredient (API) or finished drug dosage form.

• The document provides the regulatory authority with confidential, detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of one or more human drugs.

• Drug Master File or DMF is a document prepared by a pharmaceutical manufacturer and submitted solely at its discretion to the appropriate regulatory authority in the intended drug market.

• It is known as European Drug Master File (EDMF) or Active Substance Master File (ASMF) and US-Drug Master file (US-DMF) in Europe and United States respectively.

• The DMF contains factual and complete information on a drug product's chemistry, manufacture, stability, purity, impurity profile, packaging, and the cGMP status of any human drug product.

•Directive Document:

•Working documents that establish the standards for resources, processing, products & quality system.•Describe how to do it……???•Describe how to do routine work.•Several types of directive documents.•The different types are determined by the specific, functional purpose of the document in the document system.•In order to facilitate the development, production, testing and distribution of a product in a defined manner.•Reviewed and approved by both management and the individuals responsible for performing the work.

•Specifications:

A document specification contains several parts:

a description of the audience(s) for the document

a detailed outline giving the structure and contents of the document

a work plan showing who is responsible for each part of the document

what the deadlines are for completing each task.

Three purposes for document specifications:

In the workplace, formal document specifications serve three important functions:

economy of effort,

work planning,

writing organization.

Standard Operating Procedures (SOPs):

Standard Operating Procedures (SOPs) are issued to specifically instruct employees in areas of responsibility, work instructions, appropriate specifications and required records

A Standard Operating Procedure (SOP) is a set of written instructions that document a routine or repetitive activity followed by an organization.

Record document:

Protocol:

Protocols are written records clearly defining the objectives and methods that will be used for the validation programs.

An important part of the protocol is the description of the testing method including who will test the system, how they will test it and what data is to be collected and reported.

Computerized system protocols often include the three distinct stages as described in PMA reports: Installation Qualification (IQ), Operational Qualification (OQ),and Performance Qualification (PQ).

Protocol Changes

documented requirements specifying who and how changes to parameters, thresholds, and acceptance criteria are made after approval.

It is not impossible to make changes after or during testing, but these changes must be properly implemented and approved to be validatable.

What Good Documentation requires:

APPROVAL

CLARITY

REGULAR REVIEW AND UPDATE FORMAL PRESENTATION

PROTOCOL FOR DOCUMENTATION

1.Serial number of the Batch Manufacturing Record.2.Name of the product.3.Reference to Master Formula Record.4.Batch/Lot number.5.Batch/Lot size.6.Date of commencement of manufacture and date of completion of manufacture.7.Date of manufacture and assigned date of expiry.8.Date of each step in manufacturing.9.Names of all ingredients with the grade given by the quality control department.10.Quality of all ingredients.

11. Control reference numbers for all ingredients.12. Time and duration of blending, mixing, etc. whenever

applicable.13. pH of solution whenever applicable.14. Filter integrity testing records.15. Temperature and humidity records whenever applicable.16. Records of plate-counts whenever applicable.17. Results of pyrogen and/or bacterial endotoxin & toxicity.18. Results of weight or volume of drug filled in containers.19. Bulk sterility in case of aseptically filled products.20. Leak test records.21. Inspection records.22. Sterilization records including autoclave leakage test records,

load details, date, duration, temperature, pressure, etc.23. Container washing records.

24. Total number of containers filled.25.Total numbers of containers rejected at each stage.26. Theoretical yield, permissible yield, actual yield and variation thereof.27. Clarification for variation in yield beyond permissible yield.28. Reference numbers of relevant analytical reports.29. Details of reprocessing, if any.30. Name of all operators carrying out different activities.31.Environmental monitoring records.32. Specimens of printed packaging materials.33. Records of destruction of rejected containers printed packaging and testing.34. Signature of competent technical staff responsible for manufacture and testing.

STEPS IN PMD PROGRAMME

1.Identify at least two or more fairly knowledgeable persons, one each from production and QC/QA who are familiar with organization product .

2.List out manufacturing formulation departments existing or planned .

3.List out the QC /QA ,engineering,warehousing,personnel and other actives.

4.List out countries to which the product are likely to be sold/distributied and collect the specific PMD requirements .

5. Categorization of documents should be following

Documents for personal training

QC/QA. Building/factory Equipment Materials/stores Engineering Distribution.

Each category can be split into following

SOP’s Lists Charts/formats Specifications Test methods Reports

6. Design the documents-considering the following points

Contents Formatting Size and quality of paper etc.,.7. Explain the document to people concerned Train them in using the same8.Trail run the documents, study the difficulties, modify

and redesign9. Implement the document10. Review by receiving feed back from the users at

regular intervals.

General requirementsGeneral requirements

Each document should have: Have a clear title Have an identification number Be approved by authorized person have the date of issue document should not be hand written Records should be retained at least one year

after the expiry date of the finished product

Designing of documents involves the following factors :

Size of the paper Color of the paper All four sides margin must be define generally 25

mm from left and 15 mm all sides All documents must match the requirements

described in manufacturing and marketing authorization.

All documents must bear the name of the company and logo, if applicable

All documents must be approved, authorised,signed and dated by the authorized person. Title and contents of the documents must be self

explanatory. Generally every document must be review every

two years or earlier.

When you design a document, run a dummy trail of the document.

Users must be well trained in using a document Normally all records must be stored for 1 year

after the shelf life of the product .

GMP GuidelinesGMP Guidelines GMP guidelines specify certain documents to

be maintained necessarily:

1. Labels2. Specifications and testing procedures3. Records4. SOPs

LabelsLabels

Labels are used for identification or status of container, equipment and premises.

According to status of container the following color labels are used

Quarantine -- yellow Approved -- green Rejected -- red

Guidelines for labelsGuidelines for labels

Label of finished product contains

Name of the drug product List of the active ingredients, qty Net contents Batch number Expiry date Storage conditions Name and address of the manufacturer

Specifications and testing proceduresSpecifications and testing procedures

In case of pharmaceutical products we need specifications for

Active and inactive starting materials Primary ,printed and other packaging materials Intermediate and bulk products Finished pharmaceutical products

RecordsRecords

Various documents maintained in production department are

Raw material records Master formula records Batch production records Quality control records Calibration records to instrument Records for stability studies

Raw material recordsRaw material records

Schedule U shows the following particulars for raw materialrecords Date of receipt Invoice number Name and address of manufacturer Batch number Quantity received Pack size Date of manufacture Date of expiry Quantity and date of issue

Master formula recordsMaster formula records

Master formula record are defined as written procedures that give complete description of all aspects of mfg, packing,& control with intention to ensure the purity, identity quality & strength of the product.

Master formula records should be prepared by competent technical staff and should be reviewed by the heads of production and quality control departments

Master formula records should be described asFollows Name and strength of product along with dosage form Complete list of all ingredients Accurate statement of weight of each ingredient A description of containers , closures , packaging

materials A description of vessels equipment to be used in there

preparation. Processing and packaging procedures In process controls to be exercised during processing

and packaging

Quality control recordsQuality control recordsQC records must show Date of performance of test Identification of material Name of supplier Date of receipt Batch number Quantity received Quantity of sample taken Statement of result of test Signature of person who performs the test

Calibration records for Calibration records for instrumentsinstruments

The procedure for calibration records must include the following detail

Name of the instrument Date of calibration Reference standards used Other reagents or tools used Name and sign of the person who calibrated

Records for stability studiesRecords for stability studies

Procedure for stability study records Name of product Complete description of the packaging material

used Period of time during which stability study has

been carried out Condition in which product has been stored

during study

SOPSOP Sop is a defined as written documents

specifying the procedures that must be followed to carryout operations

The purpose of a SOP is to provide detailed instructions on how to carryout task so that any employee can carryout a task correctly every time.

SOPs are useful tools for training new members of staff

SOPCompany Name and Address:          

Page No: X of Y

Title :      

SOP No: Revision No: Review Period:

Prepared By Reviewed By Approved By        

   

Scope   Responsibility     Procedure

ConclusionConclusion

It is concluded that good documentation is everyone responsibility in the industry because the quality ,safety, efficacy of the product will be reflect on the documentation

Documentation is having its own importance in the pharmaceutical industry and good documentation leads to produce good quality of products

Formulation development for global fillings

THE IMPACT OF WORLD REGULATIONS TO DEVELOP AND LAUNCH HARMONIZED COSMETIC PRODUCTS

Business Strategy:

Since long time ago, we have been challenged:

“ How can we develop a cosmetic product that can have its inventory ready to be exchanged around the globe.”Same package with all information inSame formula“In other words: How to make one fit all”Understand what is required in each country to sell cosmetics

R&D Process

• Product Development

• R&D systems should be able to provide to the Formulator the ingredient’s regulation around the global/region so that only approved ones can be used

• Product Safety

• Make sure that ingredients that are not regulated are safe.

• Make sure that final formulation is safe

• Make sure claims are substantiated

Regulatory Affairs

Make sure to update database system

• Ingredients update

• Safety test requirements

• Specific country/region product registration requirements

•Words/expression restriction / forbidden

•Claims requirements

•Unique requirements

Harmonized Product

•Last but not least

•Define Manufacturing strategy

•This will drive the last regulatory requirements to have harmonized product:

•Same package•Same formula•Same label copy

•Approved in the countries according strategy

The impact of world regulation to develop and launch harmonized cosmetic products

Time to launch harmonized product is too long impacting:

•Marketing strategy

•Supply Chain strategy

•Adding Premium costs

•Service issues

ReferencesReferences

Guidelines on cGMP and quality of pharmaceutical products by “S.IYER “

cGMP for pharmaceuticals by “ MANOHAR A POTDAR “

Pharmaceutical production and management by “ CVS SUBRAMANYAM”