Handling of Highly Active Products

Objective

Main focus of this conference is on the connection of cGMPs with  safety aspects, especially on avoiding cross contamination and minimizing exposure. Recently completed projects and facilities for the production of highly potent products demonstrate the state of the art.

It will also deal with exposure & cleaning validation limits and the possibilities offered by containment technology, shown by real life examples from pharmaceutical industry including oral solid dosage forms and sterile medicinal products.

Target Audience

This conference aims at persons from production, engineering and quality, responsible for

  • Design of new manufacturing areas
  • Operation of processes containing highly potent material
  • Occupational safety
  • Cleaning concepts and contamination prevention

as well as engineering and plant-construction companies working in containment projects.

Background

Exposure to active pharmaceutical ingredients must be kept within acceptable limits. The protection of employees must be achieved primarily by technical measures and not through personal protective equipment. Several containment solutions like glove boxes, isolators, special valves and transfer ports are available. This equipment has to fit to the surrounding, the product requirements and the organisational circumstances. Therefore detailed planning is necessary.

But GMP also has requirements for contamination or the avoidance of contamination / cross contamination as far as possible (see chapters 3 (Premises & Equipment) and 5 (Production) of the EU GMP Guidelines). By introducing the PDE concept (Permitted Daily Exposure) from the European Medicines Agency, occupational medicine and GMP requirements are now based on the same scientific basis, namely on the question: how much exposure is uncritical for a person (whether patient or employee)? This important question has to be answered for both, dedicated and multi purpose equipment. And since the new Annex 1 also requires measures against cross contamination, this is also becoming increasingly relevant for sterile products. And all the more so, the more potent the starting materials or products are. What can a cross contamination control strategy look like and how is it documented?

Learn from recently finished projects and see what the state-of the-art looks like. This applies to oral solid forms as well as to liquid, sterile medicinal products.

Moderator

Dr Harald Stahl

Detailed Programme

Presentations - 28 March 2023

Principles of Assessing and Managing Occupational Health Risks in Potent Compound Handling
Dr Andreas Flückiger, formerly F. Hoffmann-La Roche

  • Legal requirements regarding worker safety
  • Assessing the hazard: potency and toxicity of the compounds
  • Occupational exposure limits and exposure bands
  • Ensuring the right level of process containment: Design exposure limits as drivers for equipment selection. The illusion of “closed processes”
  • Setting of health-based exposure limits and process containment: great benefits for GMP

Exposures to pharmaceuticals at the workplace must be controlled to below acceptable limits. For most APIs, the manufacturer himself needs to develop these limits, and compliance with them must be documented. Protection of the workers from overexposure must be achieved primarily by technical means and not by means of personal protective equipment. Equipment must have adequate containment so that the required exposure control is ensured at least in all routine situations. Existing facilities must be upgraded accordingly. The toxicological and pharmacological basis of assessing APIs with the objective of worker protection is the same as the one justifying GMP cleaning criteria and acceptance of multi-product use of a facility. Primary process containment is the key tool for the prevention of airborne cross-contamination and via the one by mechanical transfer.

Review of technical Requirements for contained Product Handling
Dr Harald Stahl, GEA

  • Product transfer- review of current possibilities
  • Sampling 1 - Review of possibilities for contained sampling
  • Sampling 2 - Examples for in-line measurements allowing to drop sampling
  • Cleaning: Examples of automatic cleaning

Case Study Pfizer: Constructional and regulatory Challenges of an OEB 4 Manufacturing Site
Gunther Bechmann, Pfizer
Prof. Christa Schröder, University Albstadt Sigmaringen

Special requirements have to be considered for planning and construction of buildings intended for manufacture of highly potent medicinal products

  • Implementation of special GMP Requirements
  • Special staff training
  • Environmental aspects

GMP Inspection Experience of Products containing hazardous Substances & Introduction to WHO’s Prequalification Program
Vimal Sachdeva, WHO

  • WHO Prequalification (PQ) history and process
  • WHO PQ of pharmaceutical products containing hazardous substances
  • GMP-compliant handling of hazardous substances
  • Challenges during GMP inspections

Case Study Hovione: Spray Drying and Continuous Tableting of highly active Materials
Dr Filipe Gaspar, Hovione

  • Relevance of Spray Drying and Continuous Tableting in the Pharmaceutical Industry
  • From risk assessment to lab development and to commercial manufacturing
  • Specific requirements for Spray Drying and Continuous Tabletin
  • Examples of lab to commercial units capable of handling potent APIs
Presentations - 29 March 2023

Cross Contamination Control Strategy in Light of the new Annex I
Robert G. Schwarz, FH Campus, Vienna

  • OHS-requirements and CCS according to the new Annex 1
  • Cross Contamination Control - the unseen stepchild of them with maybe a high potent habit
  • How to implement a compliant CCS with Containment requirements properly
  • "Close, closer, isolator - but what about RABS?" - Question from the desperate pharmacies

Case Study Lonza: Use of Single-Use Equipment for the commercial Production of highly potent ADCs
Dr Nadine Gerlach, Lonza

  • Challenges in the production of ADCs (Antibody drug conjugates)
    • GMP aspects
    • Personal safety
  • Current challenges in the use of single use components in the pharmaceutical industry
    • Multisourcing
    • Qualification of single-use materials
  • A look into the future: Single-use equipment in ADC production

Case Study Minapharm: Design of a HPAPI Biomanufacturing Facility
Dr Morcos Loka, Minapharm

  • How to apply risk management in the design of a facility for biopharmaceutical HPAPIs
  • How to achieve compliance with US & EU GMP and EHS requirements
  • What controls can be applied regarding equipment closure, flow of materials and personnel, waste management, cleanroom, HVAC
  • How to set a suitable containment strategy
  • What are the possible challenges and how to overcome
  • How to quantitatively evaluate the effectiveness of these controls

Case Study Merz: Production of sterile & highly potent Products
Fred Wulfgramm, Merz

Handling of Solids with Single-Use Systems in the chemical Synthesis of highly active Substances
Dr Rainer Nicolai, F. Hoffmann-La Roche

  • Available Equipment & Technology
  • Pros and Cons of Single-Use Systems
  • Case Studies: Experience with SUT in chemical synthesis of highly active substances

New approach for assessing Dust-Retention Performance of high-containment Systems
Dr Andreas Flückiger, formerly F. Hoffmann-La Roche

  • Continuous or periodic dust emission monitoring. Results in μg/m3.
  • Early detection of otherwise unnoticed leakage
  • Intervention before worker exposures become too high

High containment systems have generally been tested for their containment performance, for example based on ISPE’s “SMEPAC” guide. This reflects the design and performance of the equipment as it leaves the factory of its manufacturer. Over time, these systems may lose some of their containment  capability, and this is often not visible to the naked eye. The Digital Canary is a system to continuously or periodically monitor dust emissions with the objective to detect leakage before it becomes critical for worker safety. Contrary to a particle counter, it delivers the results in μg/m3. The results can serve as a trigger for preventive maintenance and can replace costly substance-specific industrial hygiene sampling. The system is compatible with a range of solid
dosage applications. The Digital Canary is being developed for additional uses.

x