Pharmaceutical Manufacturing Documentation Overview

Pharmaceutical Manufacturing Documentation (PMD)

• PMD is a complex subject, making a consolidated list of documents that meet all company requirements challenging.
• Each company's needs for PMD must be evaluated individually; one-size-fits-all solutions are not suitable.
• Organizational factors, such as manufacturing activities, country requirements, computerization level, and other considerations, must be carefully studied before designing PMD.

Steps in TMD Program

• To manage the complex PMD program systemically, identify knowledgeable personnel from production and QC/QA familiar with product profiles and requirements.
• List existing and planned manufacturing formulation departments.
• List QC/QA activities, categorized by section.
• List countries where products are sold, and collect specific PMD requirements for each country.
• Categorize the documents needed to meet the requirements, prioritizing personnel training documents, QC documents, building/factory documents, equipment documents, material/store documents, engineering documents, distribution documents, and market complaint documents.
• Further categorize documents within each main category into SOPs, lists, charts/formats, specifications, test methods, reports, one-time and recurring documents like MPCR and BPCR.
• Design documents with considerations for content, formatting, paper size and quality.
• Explain the documents to concerned personnel and train them in usage.
• Trial run the documents, identify and resolve issues, and revise as necessary.
• Implement the document.
• Regularly review by gathering user feedback.

Guidelines for Designing and Implementing PMD Program

• A document is any written statement or proof.
• PMD objectives include defining the manufacturer's information and control system, minimizing misinterpretation and errors in communication, providing unambiguous procedures, confirming task performance, allowing calculations to be checked, and tracing batch history.
• Good documentation is essential for quality assurance, linked to all aspects of cGMP.
• Documentation defines specifications, ensures personnel understand manufacturing procedures, and enables authorized personnel to release batches.
• A thorough audit trail allows investigation of suspected defective batches.
• Each document should include user company/trading name, purpose/title, document ID (unique, indicating revision), date of authorization, expiry/review date (if applicable), signatures of authorizer and preparer, distribution list, page numbers, usage instructions, reason for revision, and preparation references.
• Documents should not be handwritten, initialed for verified issues, and corrections should permit reading of original information with a reason.
• Documents requiring dates or additional information should have sufficient space designated and be clearly marked. Handwritten entries should be in permanent ink and corrections initialed.
• Instructions should be clear, precise, unambiguous, and imperative.
• Amendments should be formally authorized before use and should replace the original superseded documentation.

Product Traceability

• System should document batch history, from starting material to final product, including utilization and disposition (destruction).
• Sales and distribution records should be easily accessible and complete for recalls when necessary.

Storage and Retention of Documents and Records

• Retain complete records for at least one year post expiry date unless regulations specify longer periods.
• Store paper or film records in restricted access areas protected from tampering or loss.
• Records can be retained by computer storage systems, microfilm, or microfiche.

Retrieval of Documents

• Prepare an alphabetical list of documents.
• The list should include document name, location of availability, and person to contact for retrieval.

Disposal of Documents

• Destroy expired documents with proper record and authorization and prescribed methods like shredding or burning.

Specifications

• Specifications are parameters a material or equipment must meet. They are company-specific documents with specific contents.
• Pharmaceutical product specifications include active/inactive ingredients, primary/printed packaging, intermediates/bulk products, finished products.

Master Production and Control Record (MPCR)

• A one-time document to ensure batch uniformity.

• It must be dated, signed by one person, and independently checked and signed by a second person.

• SOPs must guide MPCR preparation.

• Summary contents: (1) product name, strength, and dosage form; (2) active ingredient name, weight or measure per dosage unit, and total weight/measure; (3) list of special characteristics (e.g., particle size, bulk density, color); (4) accurate statement of component weight/measure; (5) statement of theoretical yield; (6) description of containers, closures, and packaging materials; (7) manufacturing, control, sampling, and testing instructions; (8) precise processing location and equipment statement; (9) method/reference to handling methods, critical equipment assembling/cleaning/sterilizing; (10) specific storage conditions; (11) process controls with instructions for sampling and acceptance.

Batch Production and Control Record (BPCR)

• A recurring document, essentially mirroring the MPCR but providing a complete batch production history.
• It details all activities related to batch production and control, including dates/times, equipment/line identification, component identification, weights/measures, in-process and laboratory control results, actual yield and theoretical yield percentage, packaging/labeling inspections, and any investigation of discrepancies.

Important SOPs and Records

• Important SOPs and records need to be maintained, such as for receipt, sampling, storage, and dispensing of materials; instruments and equipment, covering, operation, and maintenance; SOP on batch numbering; Standard Test Procedures to test materials and products at different manufacturing stages; records of analyses, equipment assembly, cleaning, sanitation, maintenance, and personnel qualification; environmental monitoring; pest control; product complaints, recalls, and returns; distribution; log books for recording use, validation calibrations; procedures for retention, and document disposal.

Change Control

• Change control is a system for managing, documenting, approving, and executing changes. It prevents changes that negatively affect product quality or conflict with regulatory requirements or commitments.
• Change control anticipates changes, using indicators such as an abnormally high number of rejected products or multiple product complaints.
• The quality management unit plays a key role in reviewing, assessing the rationale, and approving all changes.
• Change control should differentiate between planned and unplanned changes.

Site Master File (SMF)

• A complete, factual overview of a pharmaceutical manufacturing site.
• It should be appropriately concise, not exceeding 100 pages.
• It should specifically include general information (organization, site information, manufacturing and other activities, product types, employee details, external assistance, quality management system), personnel information (organization chart, qualifications, experience, key personnel responsibilities, training, health requirements, clothing), site premises and equipment (description, construction and finishing, ventilation, and equipment information, calibration system, maintenance and sanitation), documentation and other essential information (Preparation, revision, and distribution of documents, relevant product quality documents, additional documents, and manufacturing/ operational procedures).