Pharmaceutical Quality Assurance & Control

• Good Manufacturing Practices (GMP) are a set of guidelines that ensure pharmaceutical products are consistently produced and controlled according to quality standards.

Pharmaceutical Drug Categories:

• Natural products are obtained from herbs, plants, roots, vines, and fungi; an example is Turmeric.
• Small molecule drugs (SMDs) are chemically synthesized products inspired by natural products; an example is Aspirin (molecular weight 180 g/mol), which reproduces salicin from willow bark and has a molecular size less than 900 Dalton.
• Biologics, also known as biopharmaceuticals, are produced by genetically engineered organisms, such as vaccines and recombinant proteins for cancer treatment; an example is Avastin (molecular weight ≈149000 g/mol), with a molecular size greater than 900 Dalton.

GMP Concepts:

• GMP is a quality assurance system ensuring products for human consumption are produced consistently and controlled to quality standards, minimizing risks like contamination and errors during production.
• cGMP means Current Good Manufacturing Practices, which involves using up-to-date technologies and systems to comply with the most updated regulations and changes.
• GMP applies to manufacturing biologics and pharmaceutical drugs, medical devices and implants (e.g., prostheses and diagnostic instruments), cosmetics, and food.

GMP Application within a Company:

• GMP applies to all manufacturing steps from start to finish.
• GMP implementation includes proper organization and personnel, with defined responsibilities and qualifications for the personnel.
• GMP incorporates equipment management including calibration and preventive maintenance, and buildings and facilities, including design, construction, and maintenance
• GMP relies on production controls to ensure all procedures and limits are followed, and that risks of contamination are mitigated.
• GMP also extends to quality control, including samples and retains, records and reports (traceability), inspections and audits, documentation, validation, packaging and labelling with proper expiration dating and tamper-proofing, as well as warehousing and distribution.

Importance of GMP:

• GMP prevents tragedies, prevents taking shortcuts, and inculcates attitudes and actions towards producing quality products.
• Production of biopharmaceutical products and medical devices are governed by GMP requirements.
• GMP knowledge is important for work in related industries.
• Good Manufacturing Practices (GMP) can be summarized with other Pharmaceutical Practices with "GxP", including Good Manufacturing Practice (GMP), Good Laboratory Practice (GLP), Good Documentation Practice (GDP), Good Distribution Practice (GDP), Good Dispensing Practice (GDP), and Good Clinical Practice (GCP).

GMP Historical Context:

• In the early 1900s, "The Jungle" revealed unsanitary conditions of the Chicago meat packing industry including slaughtered animals under insanitary conditions, sales of rotten/diseased meat, and ground meat tainted with poisoned rats and unfortunate workers.
• In 1906, the Pure Drug and Food Act was passed in response to the conditions in the Chicago meat packing industry to prevent contaminated food/meat, require truthful labelling, and create the FDA.
• In 1937 an incident occurred in which a manufacturer used diethylene glycol in preparation of Elixir Sulfanilamide, leading to more than 100 deaths, which resulted in enaction of Federal Food, Drug and Cosmetic Act (1938).
• In the 1960s, the drug Thalidomide that was used for a sleeping pill and morning sickness medication, caused over ~10,000 cases of birth defects known as Flipper Babies; this led to tighter regulation imposed for proving drug safety and effectiveness.

Regulatory Oversight:

• Regulatory bodies license and control the manufacture and sale of healthcare products, ensuring systemic conformity through GMP; each country sets its own standards.
• The FDA (USA), EMA (EU), HSA (SG) regulates GMP.
• The Medicines and Healthcare products Regulatory Agency (UK) Therapeutic Goods Administration (TGA Australia) and Pharmaceuticals and Medical Devices Agency (Japan) are other regulatory bodies
• Overall, all regulatory bodies overall principles of GMP are the same, but they differ in approach and guideline enforcement.
• Approvals from country-specific authorities are required to sell products in that country.
• Regulatory agencies inspect manufacturing plants for GMP compliance; the FDA visits USA sites without notice, while sites outside the USA get a 90-day notice; HSA visits Singapore plants with advance notice.

GMP Regulations & Guidance:

• The USA follows Title 21 Code of Federal Regulations (CFR) Parts 210, 211, 820, and FDA Guidelines.
• The EU follows EU GMPs Annex 1, 2, 13 EU Directives 2003/94/EC, 2004/23/EC.
• Australia follows the Australian Code of GMP.
• Singapore follows PIC/S Guide to GMP for Medicinal Products.
• ICH's mission is harmonizing the standards from different countries; ICH Q7A GMP (Good Manufacturing Practice) Guidance for Active Pharmaceutical produces over 40 guidelines.
• The Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme (PIC/S) established in 1995, provides a non-legal cooperative arrangement between regulatory countries with 60 members as of Oct 2024; HSA became a member in Jan 2000.

PIC/S Benefits:

• Training opportunities through PIC/S Seminars and the Joint Visits Programme, which provides a forum for regulators to train together.
• Uniform global GMP standards as the PIC/S Committee promotes uniform meaning of GMP and Quality Systems for GMP Inspectors.

Quality

• Quality exhibits a product that meets specifications, fulfilling its fitness-for-use.
• The basic elements of Quality Management are the appropriate infrastructure or “quality system", systematic actions with adequate confidence.
• Management authorizes direction regarding quality.
• All elements contribute to quality assurance.

Appropriateness of QA System:

• Appropriateness of QA System is the Responsibilities and Authorities for all managerial and personnel which is defined in job descriptions.
• A good QA system approaches and applies the Quality Standards Complying to same standards which is GMP, GDP, GLP and current regulatory guideline.
• QA production and control operations should be properly defined in documentations (Manufacturer, supplier and use of materials).
• QA should also include product sales, adhering to marketing authorization, production, and QC needs, which are authorized by an authorized person as well as self-inspection and/or Quality Audits
• QA should document reporting and tracking systems with appropriate approvals.

QA Personnel:

• A satisfactory system of quality assurance relies on sufficient and qualified personnel to carry out tasks.
• All personnel should be trained in cGMP awareness and practices, with regular refresher training and proper documentation.
• Key personnel, including heads of various departments (manufacturing/operation, quality, sales/distribution, etc., should be full-time, with heads of operation and quality being independent of one another.
• A Quality Unit has the responsibility to approve/reject incoming components and products manufactured and should be involved of all product designs.

GMP Documentation:

• GMP Documents Requiring Quality Approval include Policies, Standard operating procedures (SOPs), Product specifications, Validation protocols, Change control records, Batch records, Analytical testing methods, Raw material certificates of analysis, Calibration and maintenance documents, Non-conformity investigation reports, Product release package, and Complaint records.
• QA entrails processes for systematic analysis processes pre-planning and documented systematic undertaking.
• Quality Assurance (QA) verifies physical quality through analytical testing.

Quality Control

• Quality control relies on automated preventive measures for processes collected statistically.
• Quality Audit: A systematic, independent examination of the quality system with calibration and preventive maintenance with the purpose ensure continuous effectiveness of the quality management system
• Quality control standards must be performed within set intervals.

Documentation

• Documentation in complying to cGMP assures quality-related activities follow plans; the original copies of documentation must be accurately managed.
• Documentation includes Procedures (SOP) Records, logbooks, datasheets Protocols reports and Labels.
• Documentation serves to assure regulators that the manufacturing process complies to legal requirements and traceability for finished batches and investigations.
• Personnel signatures are documented through handwriting or encrypted, and shall only belong to that person for the actions they made.

Good Documentation Practices:

• Good Documentation Practices (GDP) provides standards to GMP execution which has complete and accurate records.
• Guiding Principles of GDP includes Accurate, Complete, Traceable, Permanent, Clear , Timely record creation, and documentation storage.
• Error regulations can be made with strike throughs made with single lines.
• Data Integrity and Accuracy of Data are key in good reporting.
• SOP (Standard Operating Procedure) documentation dictates all actions which is important in cGMP.

Standard Operating Procedures

• SOPs dictates all repeated task for an operation has a standard operation.
• SOPs Format are created with information of frequency, the Title, number, approved, the description.
• SOP writing must have a descriptive title and a concise procedure for quality.

Definitions

• The three Quality definitions are:
  • Batch/Lot: : A batch of product from beginning to end will be treated as one unit.
  • Batch Production: Each process is completed before moving onto the next process.
  • Batch/ Control number: combination that labels it as a single unit.

Records

• Records data of the product of production containing original files or electronic data.
• Record storage has a list of quality documentation that is retained for 1 year after the production and is made apparent and organized for viewing when inquired.
• Record entries should be initialed and dated.
• Batch production records contain a variety of information that are duly marked.
• After all product records are created and completed they get approved and audited.

Types of records

• Production records contain equipment status, equipment conditions, components from supplier, labels and distribution records.
• Laboratory and testing records contain data for results and experiments.

Equipment Cleaning

• Equipment Cleaning a status log on the current state and the status of the equipment (cleaning maintenance), and a log of raw materials.
• All Equipment will undergo a inventory count record stating the amount of items that passed and failed within a production.
• Production and manufacturing Records contain the process that products are produced and how long a set of cycles are manufactured along with any defects or changes.

Test your knowledge of pharmaceutical quality control and assurance. This quiz covers responsibilities of quality units, deviation investigations, contamination sources, and personnel hygiene in pharmaceutical manufacturing.