GMP Compliance Guide

Understanding GMP Compliance in Pharmaceutical Manufacturing

Within the industry, the definition of "quality" goes beyond a philosophical quest, as it has to meet the parameters of measurable industrial standards. Good Manufacturing Practice (GMP) is the global standard for determining that every medicine batch is safe, pure, and effective.
What does it entail for pharmaceutical manufacturers to obtain and maintain compliance with GMP standards? It is an all-inclusive, unequivocal dedication to every level of the operation, no matter how trivial it might seem; from air control in a production facility to the ink used in record books. This post identifies and explains the strategic benefits of partnering with a GMP compliant third party manufacturer and the advanced competitiveness that comes with it.

The Core Pillars of Good Manufacturing Practice (GMP)

GMP is not the name of one complete industrial rule, but the confluence of multiple, often conflicting, GMP guidance components, crystallized primarily by the World Health Organization (WHO), the US Food and Drug Administration (as cGMP, or current GMP), and the European Medicines Agency (EU GMP).

Sphere of Quality Management System (QMS):

Represents the formal documented system that outlines the processes, procedures and the assigned responsibility for attaining the quality standards and targets. It serves the operational brain of a GMP facility.

Sphere of Documentation and Data Integrity:

GMP requires meticulous record keeping for every action taken within a system. If it wasn't documented, it didn't happen. All data must conform to the principles of ALCOA+: Attributable, Legible, Contemporaneous, Original, Accurate, and the additional elements of Complete, Consistent, Enduring, and Available.

Sphere of Personnel Training:

All employees must be adequately familiarized and trained on their distinct responsibilities, the principles of GMP and hygiene standards, and their competencies repeatedly documented and assessed.

Sphere of Validation and Qualification:

The processes and equipment must be proven to function and perform as intended. This entails a lifecycle of qualification: Design (DQ), Installation (IQ), Operational (OQ), and Performance (PQ) Qualification.

Sphere of Quality Risk Management (QRM) Deviation and Change Control:

Any change that might affect product quality must be proposed, systematically evaluated and approved. QRM requires the principles of ICH Q9, whereby manufacturers must identify, assess, and mitigate risks to product quality throughout the manufacturing lifecycle.

The Role of Batch Records and Documentation

Batch records are the complete story of a product's manufacturing journey.

Master Batch Record (MBR)

An approved formulation and instructions document used to manufacture a specific product and batch size. The MBR serves as the authorized blueprint for production, ensuring consistency and compliance across all manufacturing operations.

Batch Production Record (BPR)

The operators used this document in real-time to record the completion of the MBR for a specific batch. It encompasses all raw materials consumption and equipment use, in-process checks, reference logs, and signatures for every critical control point.

Key Components

• Raw materials consumption tracking
• Equipment use documentation
• In-process checks and verifications
• Reference logs and critical signatures

Contemporaneous Recording

Activities must be documented as they occur. In record-keeping, the acts of backdating and pre-filling are violations of the highest order. This principle ensures the integrity and authenticity of all manufacturing documentation.

Review and Retention

The Quality Unit reviews and approves every completed BPR prior to the release of the batch. In most cases, all documents retention is for a minimum of a specified period and for several years following the expiry date of the product.

Quality Assurance Process

Comprehensive review by Quality Unit before batch release, with extended retention periods to ensure compliance and traceability throughout the product lifecycle.

Supplier and Supply Chain Controls

GMP responsibility extends well beyond the confines of the manufacturing facility, emphasizing that the manufacturer is accountable for the quality of the materials they procure as well. This includes rigorous vendor qualification, where suppliers of critical raw materials must undergo thorough audits and performance reviews to ensure they meet GMP standards.

Each batch of supplied material must come with a Certificate of Analysis (CoA), which is verified alongside in-house testing to confirm its quality. To combat counterfeiting and ensure traceability, compliant companies employ track-and-trace systems, allowing each product unit to be traced from the factory to the pharmacy.

The Validation and Qualification Lifecycle

Validation is the documentation to prove that a process consistently achieves a result that meets the specified parameters.

Process Validation (PV):

As described in ICH Q8 and other frameworks, this is the process of data collection and evaluation from the process design to commercial production to prove the process is capable of consistently delivering a quality product.

Cleaning Validation:

Evidence needed to prove that a procedure for cleaning that removes residues of the prior product is effective to prevent cross-contamination.

Analytical Method Validation:

Certifies that quality measuring tests for a product are valid, reliable, and accurate.

Continuous Improvement and Oversight

GMP compliance is not a one-off endeavor; it is a sustained state of vigilance.

01

Annual Product Reviews

An annual review of a product's performance, including an analysis of batch data, deviations, changes, and stability results, to manage trends and improvement opportunities.

02

Management Review

Review of performance for Quality Management System (QMS) by the senior leadership is essential for resource allocation, maintenance of system effectiveness, and resource allocation.

03

Pharmacovigilance and Complaint Handling

A system to receive, evaluate, and respond to product complaints, including adverse event reports, must be documented and adhered to.

Why Partnering for GMP Compliance Makes Sense

For many brands, the solution is pharmaceutical third party manufacturing. Instead of developing this intricate system independently, they can collaborate with an expert.

Cost Savings:

Avoid the immense CapEx on facilities and equipment, which can then be converted to a predictable OpEx.

Scalability:

Instantly available the ability to adjust production levels to meet market needs.

Access to Technology:

Collaborate with other firms on investments for advanced technology in areas like sterile manufacturing, handling high-potency APIs, and continuous manufacturing.

Speed and Flexibility:

A partner's established quality systems and specialization can be used to streamline the marketing of the product.

Shared Risk:

A contract manufacturer shares some responsibilities related to operational management, inspections, and regulatory compliance.

Your Checklist for Selecting a GMP-Compliant Partner

What steps will you take to guarantee the quality of a third-party manufacturer? It begins with comprehensive due diligence.

Certifications:

Ascertain the relevant endorsements, including WHO-GMP, cGMP, and others such as EU GMP and ISO 9001.

Inspection History:

Conduct research on the manufacturer's inspection record with the FDA and other regulatory authorities.

Quality Metrics:

Request their OOS rate, the average time for CAPA closure, and their first-pass yield percentage.

Data Integrity Controls:

Assess their ALCOA+ compliance and audit systems for any gaps.

Technical Capabilities:

Confirm whether the manufacturer has the relevant technology and knowledge for your product.

Production Capacity and Lead Times:

Ensure their production timeline aligns with your forecast to avoid capacity issues.

Tech Transfer Process:

Examine how they will transfer your product seamlessly from development to their facilities.

Partner with a Leader in GMP Compliance

The process of acquiring GMP compliance entails a high level of complexity coupled with a costly and continuous commitment to resources. This process is what, for the most part, isolates organizations with reputable standing in the sector from those without.

At Monark Biocare, the core of our internal operations is the adherence to high compliance and GMP quality systems. Reach out to us for more information about our third-party manufacturing and PCD franchise opportunities.