GMP Services for the Pharmaceutical Industry

Author: Sabine Stolley

Commissioning and Qualification
Commissioning and Qualification (C&Q) applies Good Engineering Practice (GEP) into design and construction and integrates GMP qualification principles.

General Principles & Practices

Commissioning & Qualification (C&Q) focusses on the identification on critical design elements (CDEs) in terms of critical quality attributes (CQAs) and critical process parameters (CPPs). The objective is to comply with GMP regulations to ensure the product’s safety and quality.

The “Standard Guide for Specification, Design, and Verification of Pharmaceutical and Biopharmaceutical Manufacturing Systems and Equipment (ASTM E2500)” applies Good Engineering Practice (GEP) to commissioning and qualification of process facilities regarding the production of medicinal products.

Commissioning and Qualification combines GMP system qualification principles, into design, construction, assembly, installation, testing and documentation to manufacturing systems.
Main C&Q Phases

Design Review and Design Qualification

C&Q Testing and Documentation

C&Q Acceptance and Release

Main C&Q Requirements

URS

System Classification

System Risk Assessment

System Risk Assessment

Identify system risks in terms of product and process quality

Evaluate and analyze the identified risks

Define risk controls in terms of CDEs (critical design elements)

Define system alarms

Link testing activities to CQAs and CPPs
Build C&Q in the process facility setup!

Process line and process facility qualification (e.g. Sterile Fill Line Equipment) for sterile pharmaceutical manufacturing is one of the most critical assets. For aseptic manufacturing in compliance with cGMP, EU GMP Guide Annex 1, FDA guidance, and ISO 14644 principles are applicable.

Get more Info on Qualification Processes
2026-09-09
Process Equipment Qualification
Process Equipment Qualification is the verification that the equipment is properly designed, installed and operates within defined specifications as devised and specified in the URS.

About the GMP requirements to equipment qualification!

The pharmaceutical industry requires GMP compliance with regulatory authorities such as the U.S. Food & Drug Administration (FDA) or European Medicines Agency (EMA) to receive the manufacturing authorization. Equipment qualification is part of the GMP requirements and follows an elaborate qualification process.
General Principles & Practices

What is process equipment?

The manufacturing of biotechnological-derived medicinal products involves several process steps from upstream to downstream operations. Various process equipment is used for the bioprocessing of biopharmaceuticals and immunotherapies.

The process equipment varies from standard to complex equipment and devices used for production. Equipment used in a GMP-related environment should be suitable and should not present any hazard to the product. The location and installation of the equipment should be adequate to minimize risk and contamination.

Why is equipment qualifcation necessary?

The objective of process equipment qualification is to verify the fitness for purpose for its intended use and to ensure that process equipment meet their specifications as devised in the URS.

Implementation of equipment qualification

The qualification process outlined in the qualification plan include URS, risk assessment, and lifecycle management.

Process equipment should be qualified according to the Qualification Phases (DQ, IQ, OQ, PQ), calibrated, inspected and maintained at defined intervals to ensure adequate performance. Associated computerized systems (CS) should be validated to verify data integrity and data security.

When is qualification needed?

Regulatory compliance with Good Manufacturing Practice (GMP)

New equipment installation

Equipment modification

Maintenance or repair

Change in the manufacturing process
Get more Info on Qualification Processes
Key Activities

Coordination, monitoring and participation in maintenance, calibration and qualification activities in all GMP areas (quality control, manufacturing, IT-infrastructure).

Contributing to calibrated, maintained and qualified process equipment in compliance with GMP, FDA, EMA, and ISO standards.

Managing the GMP lifecycle: planning, execution, review, approval, and documentation.

Coordination, participation and contribution to commissioning and qualification operations with QC, QA, Manufacturing, and IT (DQ, IQ, OQ, PQ).
Qualification Services
2026-09-08
Process Validation
Process Validation Studies for Biologicals

FDA’s Definitions on Process Validation

Establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product, meeting its predetermined specifications and quality attributes.
General Principles and Practices

Why Process Validation Studies?

Process validation studies verify that the manufacturing process is under control and operates within defined specifications. Process validation contributes to confidence in product and process quality and ensures compliance with GMP to receive the manufacturing authorization.

Validation studies apply to drugs, biologicals, drug substances, or active pharmaceutical ingredients. The strategy to process validation should be laid down in a process validation plan.

Current scientific knowledge and the accumulated data collected during drug and preclinical development, quality control and manufacturing processes should be included to the validation studies.

Product Characterization

The objective of product characterization is to contribute to a better knowledge of product-biology and structure-function relationships. The biological product is characterized by its biological, physico- and immunochemical properties, and by purity and impurities.

However, the assessment of biological properties plays a major role in establishing a characterization profile. When defining critical product quality, these properties add quality characteristics and support product safety.

Product characterization analysis are mandatory GMP requirements for release and marketing authorization according to ICH Q6B.

Risk Assessment and Lifecycle Approach

The risk assessment identifies and provides scientific knowledge about potential quality risks. Quality risks associated with biotechnological-derived products are highly dependent on the manufacturing process, the protein itself and the manufacturing facility and environment.

The assessment shall follow the impact of potential risks in terms of critical process parameters (CPPs) and critical quality attributes (CQAs) and applies over the product and process lifecycle.
About Bioprocessing of Biological Products

Currently biopharmaceuticals and immunotherapies are being developed to fight against cancer, autoimmune disorders, infectious diseases and several other medical conditions. Biopharmaceuticals are proteins, mainly derived from living organisms or systems.

The basic science behind all biopharmaceuticals is the use of recombinant DNA technology. The cell consists of cell membrane, nucleus and cytoplasm. The nucleus contains the genetic information in form of the so-called DNA. Proteins are made within the cytoplasm. So how do we get from the nucleus to the cytoplasm? The process is called the “protein biosynthesis”.

It starts within the nucleus with the transcription of DNA into mRNA. The mRNA now serves as a template for the protein synthesis and moves to the cytoplasm. Here are the ribosomes, where the final protein is synthesized.

Genes, containing the genetic information in form of DNA sequences code for proteins or have other regulatory cell functions. The cell activates only those genes, required to produce specific proteins.

Nowadays, it is possible to identify the genetic sequences that control the production of these proteins. These genes are then isolated and duplicated on a large scale to produce the desired protein which is then extracted, purified and used for the production of the biopharmaceutical item, as they have come to be known.
Summary

Specifications, validation parameters and the acceptance criteria represent the core element of your validation studies.

Specifications must be established before process validation is performed.

When establishing specifications, expertise from drug development, drug manufacturing and quality control should be incorporated into validation and qualification processes.
Hands-on Experience

We offer expertise in upstream and downstream operations, product and process specific. We contribute to critical in-process controls, validation parameters and their respective acceptance criteria, tests used and the extent of testing.
Contact Stolley Engineering
2026-07-17
GMP Compliance Consulting
Compliance with GMP is mandatory for all medicinal products to receive the manufacturing authorization.
Why do we need Good Manufacturing Practice (GMP) ?

Pharmaceutical products are subject to high quality standards as part of submission for regulatory approval. Among these are: reporting adverse drug reactions; monitoring clinical trials and conducting inspections of manufacturers; compliance with good clinical practice (GCP); good manufacturing practice (GMP); good distribution practice (GDP), and good pharmacovigilance practice (GVP).

What is the Manufacturing Authorization?

For their manufacture, distribution and marketing authorization, a manufacturing license is required. Therefore, for a drug manufacturer, the manufacturing authorization is an essential GMP property.

About Qualification and Validation

Qualification and validation are key GMP requirements for the implementation of those quality standards. Validation operations, especially in producing sterile biopharmaceuticals, can be very challenging. The procedures are arduous and requires conscientiousness and commitment, knowledge and experience, as there are predetermined specifications and regulations to meet.
What makes biologicals unique and different?

Proteins can be 100 to 1000 times larger than chemically synthetized small molecules. Due to their large size and complex structure, biopharmaceutical production entails complex manufacturing processes. They are highly sensitive to modification during and after production.

The manufacturing process can affect many parameters, including amino-acid structure, side chains, post-translational processing and tertiary and quaternary structure. Changes could have a profound effect on protein function.

Therefore, biopharmaceuticals are different from synthetic small molecules in terms of molecular size, three-dimensional shape, and process specific impurities. The formulation of the final product is distinct in terms of excipients, bioactivity and stability.

Inconsistencies during manufacturing can lead to inter-batch variations and inconsistency of efficacy. Regarding the manufacture of biopharmaceuticals, the control of quality, safety and efficacy especially in terms of “batch-to-batch” consistency is more complex and demanding.

The responsibility of the regulatory authorities, as part of their review, is to inspect the manufacturing process and the manufacturer’s control strategy for these product variations.

Establish Product Regulations
Product Safety

Microbial agents

Tumorgenicity

Pyrogenicity

Product Characterization

Identity

Purity

Impurities

Potency

Quantity

Manufacturing

Process Control

Validation Program

Qualification Program

Quality Control Tracking

Quality Assurance Tracking
GMP Compliance Guidance
U. S. Food & Drug Adminstration (FDA)

European Medicines Agency (EMA)

WHO
About Stolley Engineering
2026-07-16
Computerized System Validation (CSV)
The Pharmaceutical Industry is subject to GMP regulations in which CSV is part of System Qualification.

About CSV?

Computerized System Validation (CSV) verifies that the computerized systems operate within its specification and acceptance criteria as defined and specified.

Data Integrity and ALCOA+Principles

9 Principles govern Data Integrity:

ALCOA is the abbreviation for: Attributable, Legible, Contemporaneous, Original, and Accurate. This term was originated by the FDA and incorporated into the guidelines.
Methods and Principles

About Computerized System Validation (CSV)

Manufacturing facilities, analytical instruments, devices and utilities used for quality control, drug manufacturing or drug development are these days mostly combined with computerized systems. A computerized system (CS) describes a hardware with software combined applications. According to GAMP 5, the software is categorized into groups to determine the scope of validation.

GMP Compliance with CSV

IT-Infrastructure is subject to validation regarding a GMP-related environment. CSV principles include GMP regulations e.g. FDA 21 CFR Part 11, GAMP 5, EudraLex Vol. 4 Annex 11, EudraLex Vol. 4 Annex 15, Datatype, ALCOA+ principles, and a risk-based system classification. CSV verifies that computerized system functions reliably and satisfying regulatory GMP requirements throughout the system lifecycle.

User Requirement Specification (URS)

User requirements, system specifications and laboratory needs should be specified in the User Requirements Specification (URS). Validation specifications and the associated acceptance criteria should be established on a risk basis.

Software Categories

Due to a variety of software applications, from firmware, infrastructure software, non-configured and configured products to custom applications, the software is classified. According to GAMP 5, the software is categorized into groups to determine the scope of validation.

Integrated Qualification

Instrument and process equipment qualification follow an integrated approach which combines the qualification phases (DQ, IQ, OQ, PQ) into CSV. The purpose to combine CSV and system qualification is to save time and effort.
Summary

Validation of computerized systems should be risk-based and throughout the entire system lifecycle. A cross-functional validation team should be formed and responsibilities such as System Owners, Qualified Persons, and Process Owners clarified.

CSV and Data Integrity Services
2026-07-14
Analytical Instrument Qualification
Analytical Instrument Qualification verifies that the instruments and devices operate within its operational specifications as defined and specified.

About Analytical Instruments

Analytical instruments and devices are essential for manufacturing and quality control of biopharmaceuticals. Most of these instruments link metrological and software-controlled functions. QA is responsible for assuring that their instruments are suitably qualified.

Analytical Instrument Qualification in compliance with USP <1058>

In 2008 the US Pharmacopeia (USP) implemented the general chapter <1058> on Analytical Instrument Qualification (AIQ) originated by the American Association of Pharmaceutical Scientists (AAPS).

This chapter was updated in 2017 to propose an integrated approach to AIQ and Computerized System Validation (CSV) together with GAMP.

The USP <1058> has become an important document since it is the only risk-based regulatory guidance regarding analytical instrument qualification (AIQ).
System Classification

To determine the extent of qualification the systems are classified into categories depending on their complexity and the criticality on its intended use.

Group A

Group A includes the simplest standards devices and instruments such as magnetic stirrer or vortex mixer which are used without measurement capability. Their handling is simple and self-explanatory. The quality of product and process will not be affected by this category and therefore qualification activities require only the basics.

Group B

Group B includes instruments which are more complex and provide a measurement capability or a condition that may affect a measurement, for example a pH meter and oven or incubator. These instruments may have firmware but are not software-controlled. The extent of qualification activities depends on criticality regarding critical quality attributes (CQAs) and critical process parameters (CPPs) which shall be analyzed by a risk assessment.

Group C

Group C includes complex analytical instruments with software-controlled measurements and analysis such as HPLC, mass spectrometer or flow cytometer. This category requires the highest quality standards. Their qualification is elaborate and labor-intensive. It also includes the computerized software validation (CSV) which is even more challenging and demanding.
Why Qualification and Computerized System Validation (CSV)?

Most analytical instruments and process equipment are combined with computerized systems and contribute significantly to datasets. Software must be categorized and specified, computerized systems must be specified and both must be validated. GMP-regulated laboratories require data to be accurate, complete, reliable and consistent.
Regulations and Guidelines

USP <1220> Analytical Procedure Lifecycle

USP <1058> Analytical Instrument Qualification

Eurachem Guide: Analytical Equipment and System Qualification

EU GMP Guide Annex 15

GAMP 5

FDA 21 CFR Part 11

EU GMP Guide Annex 11

ALCOA-Principles
Summary

Analytical instruments should be qualified, calibrated, inspected and maintained at defined intervals to ensure adequate performance.

Qualified instruments contribute to client’s confidence that analytical instruments used for quality control perform suitably according to their intended use.

The devise of a thorough URS is of utmost avail and influences the outcome of the qualification, as the URS is linked to the operational qualification (OQ).

However, user requirements and system specifications are not necessarily defined equally between supplier and laboratory. Keep in mind that the instrument testing performed in the OQ aims to satisfy regulatory quality standards.

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Qualification Services
2026-05-07
Bioassay Validation
Design, Development and Validation

Bioassays Definitions

A bioassay is a test procedure used to determine the biological activity and to verify the mode of action of a protein or advanced therapy medicinal product (ATMP), by using a biological substrate e.g. living cells, or target receptors.

About Bioassays

Due to the complexity of biopharmaceuticals and their complex manufacturing process, bioassays are one of the most challenging parts of your quality control program. Heterogeneity is a key issue and impact the product quality in terms of batch-to-batch consistency.

Given these circumstances the testing of the biological activity belongs to one of the most challenging analyses within your bioassay procedures in terms of batch release and for commercial distribution of drug products.
United States Pharmacopeia (USP)

USP <1032>: Design and Development of Biological Assays

USP <1033>: Biological Assay Validation

USP <1034>: Analysis of Biological Assays

USP <111> : Design and Analysis of Biological Assays
Methods & Applications

General applications of biological assays include characterization of biological properties, as describe in ICH Q6B, to support stability and comparability studies, batch release of samples, and to evaluate changes in manufacturing processes. Bioassays can be cell-based or cell-free. Cell-based assays refer to the use of living cells for the analysis.

Cell-based Assays

Cell-based bioassay using cell lines, derived from tumors, immortalized cells or created by cell line engineering, to study cellular response to the protein of interest. The cellular response depends on the mode of action of the desired protein.

Such responses include cell proliferation assays, apoptosis assays, cytotoxicity assays, or antibody-dependent cellular cytotoxicity assays (ADCC).

Potency Assays

The objective of potency assays is the determination of the relative potency, in which the biological activity of an analyte is analyzed by comparing the dose-response curve to the activity of a reference standard material.

ADCC Assays

Antibody-dependent cellular cytotoxicity assays.

Assays for Drug Screening and Target Validation

Drug receptor interactions play an important role in drug delivery, tumor metastasis, and immune response. Assay development has become a powerful tool for drug screening and target validation studies as part of drug discovery and drug development.
Florescence Activated Cell Sorting (FACS)

Florescence activated cell sorting (FACS) and flow cytometry analysis are widely used for cell-based assays, potency or ADCC assays, to determine the biological activity and the mode of action of biological products or ATMPs.

Implement GMP Regulations
FDA and CBER Regulation

Potency Tests for Cellular and Gene Therapy Products

Cell and Gene Therapy Products

Cell and Gene Therapy Guidance
Hands-on Experience

Our validation engineers, who are well-qualified, specializes in cell and molecular biology, allowing us to contribute to the design, development and validation of cell-based assays, potency assays, ADCC assays, and assays for target validation and drug screening, to support marketing authorization and GMP release of samples.

Bioassay Validation Services
2026-03-20
GMP Qualification Process
What is GMP Qualification?

Qualification is the verification through documented activities that an instrument, process equipment, or process facility involved in manufacturing and quality control of medicinal products is properly designed and installed and operates within predefined specifications.

What is the purpose of GMP Qualification?

The purpose of qualifying process equipment or analytical instruments is to verify suitability for the intended use and to ensure that process equipment, devices or facilities meet their specifications and the associated acceptance criteria as defined and specified.
General Principles and Practices

GMP Qualification is an intricate process consisting of four main phases: DQ, IQ, OQ, and PQ. Qualification is part of validation. Equipment, instruments, systems, and devices are qualified, processes, procedures, and methods are validated.

Design Qualification (DQ)

The selection and purchase of a new instrument, process equipment, or process facility shall follow a documented decision process. The decision is based on the needs related to the intended purpose.

General DQ activities

I Planning

Design stage

URS, FS

System Classification

Risk Assessment

II Procurement

III Suppliers Work

FAT

SAT

Installation Qualification (IQ)

The IQ verifies the correct implementation of the requirements defined in the design qualification (DQ) during the assembly and installation of the equipment. The verification of the installation qualification (IQ) is basically performed on the basis of the previously devised URS.

General IQ activities

Instrument delivery

Description

Utilities/Facility/Environment

Assembly and installation

Software installation, network, and data storage

Installation verification

Operational Qualification (OQ)

OQ verifies that the process equipment, process facility, or analytical instrument operates within its specified operational specifications as designed and installed.

OQ follows the IQ

OQ verifies the URS

FAT and SAT should be incorporated into testing activities to avoid retesting

Performance Qualification (PQ)

PQ verifies that the process equipment, process facility, or analytical instrument operates consistently and reproducibly within predefined performance specifications and acceptance criteria under actual conditions of use.

PQ therefore ensures the fitness for purpose of the process equipment or process facility under actual conditions of use.
User Requirement Specifications (URS)

User requirements and system specifications are devised in the User Requirements Specification (URS). The user requirements refer to the laboratory needs and the technical and operational requirements of the system.

Specifications must solve every part of the problem described in the URS. Requirements and specifications must be testable.

The URS is an essential regulatory GMP document which is directly linked to risk assessment and qualification. The devise of a thorough and intelligent URS is of utmost avail as the URS influences directly the outcome of the qualification process.

Instrument Calibration

Calibration is a test procedure to establish the relationship between the output and input variables, i.e. the measured value and the corresponding true or correct value using a reference standard to identify the deviation of a test device (e.g. test instrument, analytical instrument, system).

FAT

For complex process line or process facilities the framework is extended to include functional specifications (FS) and factory acceptance testing (FAT). FAT is performed by and at the vendor’s location. The primary objective is to ensure that the system meets the functional and operational specifications as devised in the URS. FAT may include all activities from commissioning to qualification (DQ, IQ, OQ). FAT should be incorporated into the qualification operations where possible.

SAT

Site acceptance testing (SAT) includes analytical instrument installation, process equipment installation and start-up which are normally undertaken in IQ and OQ. The equipment is retested when installed at the manufacturing site by the vendor. Some of the SAT activities may be satisfied and do not need to be repeated by the manufacturer. The documentation can be incorporated into the qualification process.

Summary

The use of qualified instruments is mandatory and part of good manufacturing practices (GMP) as required by regulatory authorities such as the U.S. Food & Drug Administration (FDA) or European Medicines Agency (EMA).

The purpose of qualification and validation is to contribute to customers’ confidence that the instruments and equipment perform suitably according to their intended use.

For GMP-related environments such as the pharmaceutical industry and treatment centers for ATMPs, qualification and validation are essential GMP requirements to confirm GMP compliance.

Lean GMP Validation
2026-02-12
Lean GMP Validation Concept
Lean GMP – Effective Implementation

The refinement and optimization of implementing GMP quality standards requires daily teamwork in different operation units and disciplines.

Designing validation and qualification concepts, quality control, quality assurance, manufacturing and IT, work at its best closely together in qualification or validation teams.

When we develop those validation strategies, we apply the Lean GMP Validation Concept. This helps us to follow refinement and reduction but keep to the regulatory expectations.

For our clients, it saves time and money by avoiding unnecessary, time-consuming, and costly validation and qualification activities. In regular project meetings, we develop and optimize the approach on implementation of qualification and validation concepts.

Our validation engineers are equipped with mind and reason to establish the objectives of your validation and qualification strategy.

About Stolley Engineering

Why Lean GMP?

Lean GMP validation aims to emphasize on an effective and efficient validation or qualification strategy to avoid time-consuming and costly Qualification and Validation activities.

Risk Assessment

Emphasize your qualification and validation strategy risk-based and focused on critical quality attributes (CQAs) and critical process parameters (CPPs).
Lean Validation Strategy

Form interdisciplinary validation team

Define precisely the validation activities

Devise precisely an intelligent User Requirements Specification (URS)

Incorporate SAT and FAT into qualfication phases

Precisely specify risk assessment

Qualification Services
Summary

When establishing the validation strategy remain focused and use common sense to establish the validation and qualification objectives.

Keep to the Lean Validation Strategies. This helps you to avoid costly and time-consuming retesting.

Precisely define your validation activities. Devise an intelligent URS and risk analysis. Avoid retesting where possible. Make the documentation as lean as possible.

Contact Stolley Engineering
2025-11-04