Good Manufacturing Practices (GMP)

For a temporary project or as a temporary manager, I would be happy to support you in the confident and successful implementation of demanding projects in quality management or in a direct line function. 

If there is a lot of work to be done in a confusing situation, things have to be done quickly or a vacancy needs to be bridged, I am happy to bring in my independent expertise with a strong implementation orientation in order to achieve GMP compliance again as quickly as possible.

DETAILS …

If you want to establish a new contract manufacturer or a new testing laboratory in your company, extensive qualification work is required. I have many years of experience in qualifying outsourced activities and can carry out individual audits worldwide for you or organize the complete qualification program for you. 

In a first step, the qualification status of the contract laboratory or contract manufacturer is determined with the aim of identifying potential risks in the supply chain. Appropriate qualification measures will then be determined in close consultation with you.

Carrying out individual audits

• Coordination with the company to be audited
• Audit preparation
• Execution
• Documentation

Audit management

• Risk ranking
• Prioritization
• Preparation, implementation and documentation
• Tracking corrective actions
• Contractual regulations

Audits can be carried out according to EU-GMP, US-cGMP, WHO-GMP standards or as a combination of the standards. 

Mock audits can also be carried out to prepare for customer audits and authority inspections, also at contract manufacturers or testing laboratories. Based on the observations, recommendations are then made to improve the compliance status.

The pharmaceutical company is obliged to establish supplier qualification for suppliers of raw materials and starting materials. It should be determined based on risk which elements are used for each supplier. I have decades of experience in auditing suppliers worldwide:

• I establish a GMP-compliant system for supplier management including qualification of new and existing suppliers, questionnaires, quality contracts and continuous supplier evaluation
• More than 100 audits carried out worldwide according to international GMP standards
• I can take care of the complete audit system
• SOPs for supplier management

If an important customer audit or an authority inspection from home or abroad is expected, I can optimally prepare your company for this event by carrying out an as-is analysis of the company's GMP status during a mock audit, discuss with you corrective and preventive measures and summarize the results in an audit report (Inspection Readiness Support). Thanks to my many years of experience, I know the inspectors' questioning techniques and can specifically train your responsible employees so that even trick questions can be identified and answered clearly and unambiguously.

Regular training of employees in the GMP area is one of the most important prerequisites for achieving GMP compliance and minimizing the error rate. GMP-Advice carries out in-house training in groups of up to 20 people at your company. One advantage of my training programs is that I adapt the programs, training content, workshops and methods to your specific wishes.

The most popular topics for in-house training modules are:

• Good Manufacturing Practices
• Correct documentation, labeling
• Personnel and production hygiene
• Basics of microbiology
• Data integrity

Digitalization is also progressing in the pharmaceutical sector and will require essential changes in operational business. In addition, authorities have increasingly focused on the issue of data integrity in recent years. 

The ALCOA+ principle (data must be attributable, readable, contemporaneous, original, precise, complete, consistent, permanent and available) must be implemented as an important component for the entire life cycle of stored data. GMP-Advice takes stock of your company data, highlights specific weak points and suggests solutions.

Risk-based decisions are the basis of modern pharmaceutical quality management. The International Council for Harmonization (ICH) has published ICH Q9, Quality Risk Management. GMP Advice supports you in establishing easy-to-use quality risk management in your company by drafting the relevant instructions or adapting existing ones.

Risk analyzes should be applied in the early phase of product development within a product life cycle, as cost/benefit optimization is most economical in the development phase (preventive error avoidance). The later an error is discovered, the more difficult and costly it becomes to correct.

Depending on the complexity of the topic, forms for carrying out simple risk assessments as well as those for complex topics (e.g. FMEAs, Failure Mode and Effects Analysis) can be used. As a rule, the influence on the process, the probability of detection and the frequency of errors are determined.

The individual steps are.

• Selection of the methodology for carrying out risk analysis
• Identification of individual risks
• Determination of key figures (e.g. RPN, risk priority number)
• Definition of measures to minimize risks
• Determination of key figures according to the definition of measures
• Risk minimization and control measures
• Determination of risk acceptance with justification
• Communication of risks

In this way, you can provide customers and authorities with proof at any time that you have made critical decisions in a comprehensible, transparent and risk-based manner.

Are you currently in the transition from an R&D-oriented business to a manufacturing company that is planning the first batches for use on humans and therefore has to produce them under GMP? GMP-Advice has many years of experience in applying the GMP guidelines for the production of clinical test samples and will accompany you on this journey and ensure that you take into account all compliance-relevant aspects, starting with specifications for raw materials and system qualification up to a release procedure for your product.

The establishment of a management review in accordance with the requirements of the ICH Q10, Pharmaceutical Quality System, is an official expectation and enables management to get an immediate overview of the suitability and effectiveness of the pharmaceutical quality system and of all important, GMP-relevant business processes, define measures to optimize GMP compliance and thus achieve continuous quality improvement.

GMP Advice supports you in implementing the management review:

• Definition of key performance indicators (KPI)
• Visualization of the KPIs
• Identify appropriate actions with priorities
• Assessment of the status of the quality system
• Writing a SOP

The efficiency and functionality of the quality systems is a fundamental prerequisite for GMP compliance. There should be tailor-made solutions that are adapted to the size and structure of the company.

On the one hand, GMP Advice supports the introduction of such systems, and on the other hand, a critical review is carried out with particular attention to documentation in order to make the quality systems leaner and more effective:

• Deviations, issuance of reports
• Corrective and preventive Actions (CAPA)
• Change control
• Process validation incl. revalidation
• Cleaning validation
• Equipment qualification including requalification
• Review computerized systems
• Internal audits
• Audit trail review
• Product quality review (PQR)
• Batch Record Review
• Batch release (preparation, documentation)
• Structure and organization of GMP documents 
• Individual support on site

DETAILS …

The quality oversight refers to the quality unit's overview of all GxP processes of the quality system. Quality oversight is a central component of the pharmaceutical quality system for the FDA. 

Your quality system must have sufficient internal control to ensure the quality of pharmaceutical products. Official inspections are increasingly concentrating on monitoring that this self-control works within the framework of the pharmaceutical quality system. It is not uncommon that quality oversight concepts are required during FDA inspections. I will work with you to develop a coherent and plausible system with which you can demonstrate the functionality and thus the self-control of your quality systems.

Many pharmaceutical companies are required to create a site master file in accordance with EudraLex or a quality manual for regulatory purposes and authority inspections. GMP-Advice creates or updates such documents for you in accordance with the specifications.

If you want to use Microsoft Excel and/or Access in a GMP environment in your company, you are obliged to validate these applications before use and to implement the life cycle concept according to the GMP regulations, when the following properties respectively functions are included:

• Simple Boolean functions (e.g. if…then/else loops, S-reference), statistical functions, user-defined queries and reports, complex templates (multiple linked table operations)
• Complicated reference functions, nested (>3) Boolean functions, networked spreadsheet applications, macros/functions (VBA/VB), multiple system sources/interfaces.

GMP-Advice creates simple but also complex applications according to your wishes and specifications and supports you or creates corresponding life cycle documents completely independently, which can consist of the following parts depending on their complexity:

• User requirements and functional specifications
• Risk-based assessment
• Validation plans, test documents
• Source code review
• Traceability matrix
• Assessment according to 21 CFR Part 11
• Technical documentation
• System description / installation instructions
• User manual
• Security management, archiving, change management

I can also create relevant SOPs with templates and protocols describing the life cycle concept.

This means I can guarantee that such validated and documented applications work securely and error-free and can withstand any critical examination during an official inspection and a customer audit.

In many cases, documents for regulatory purposes must be created very quickly in order to meet relevant deadlines and keep the time until a new product is brought to market as short as possible. GMP-Advice will be happy to support you in the creation of regulatory documents such as process descriptions.

Do you intend to compare the contents of regulatory dossiers with the actual conditions on site as part of a compliance initiative? GMP-Advice has years of experience in such compliance projects and carries out such projects on behalf of customers.

If you intend to optimize GMP processes in the value chain in terms of effectiveness and efficiency in order to simultaneously increase productivity, reduce costs and improve quality through robust and optimal processes, then GMP Advice can support you in this process, also together with management consultants to ensure that GMP issues are adequately addressed.

The Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES), signed in 1973, is an agreement on international trade in endangered species of wild fauna and flora to protect against excessive exploitation. CITES grants protection to more than 37,000 species of animals and plants, regardless of whether they are traded as living specimens, their parts or products made from them.

The Federal Agency for Nature Conservation is the German enforcement authority for the implementation of the Washington Convention on Endangered Species (WA=CITES) in the Federal Republic of Germany.

If you intend to import a plant or animal species protected under the CITES agreement into the EU in order to obtain a pharmaceutical product from it, then GMP Advice can support you by completing all the necessary formalities such as the application for import at the Federal Agency for Nature Conservation.