Current Pharmaceutical Containment Issues

Transcription

1 Current Pharmaceutical Containment Issues

2 Statutory Requirement It is the duty of every employer to carry out an assessment of the risks associated with the use of a carcinogen or mutagen in the workplace and take steps to control such risks by eliminating or minimizing exposure. Economics should not play a role in putting in place control measures. Whatever technology is currently available in the marketplace should be employed to reduce employee exposure to a carcinogen Health and Safety Authority, Dublin

3 Defining the Concept What is Containment? The design and implementation of engineering controls for use with manufacturing, pilot plant and laboratory operations, to minimize the emission of substances into the work environment with the goal of limiting potential employee exposure. The goal is to control both air and surface contamination. Product People Work Environment

4 Containment History 1970 s recognition the pharmacological effects from therapeutic agents are undesirable : May increase risk of accidents Potential adverse interactions Unsupervised or prescribed administration Drug tolerance or hypersensitivity Not specifically regulated by government or consensus group. Major pharma companies established internal occupational limits.

5 How Potent Compounds Enter the Body Ingestion through mouth and nose Transdermally very effective when mixed with certain solvents Mechanical transfer Inhalation Intravenously from accidental puncture Cross contamination Inhalation 10 M 3 day typical OEL is based on this route Mechanical transfer to mucous membranes on clothing, equipment and feet can transfer material to the home and children Ocular Ingestion through mechanical transfer from the hands Absorption exposure through the skin Intravenously as a result of sharp object penetration contaminated with the product

6 Typical Pharmaceutical Containment Program Elements Development of Occupational Exposure Limits API, key intermediates OEL provides basis for handling & containment design Performance Based Exposure Control System When OELs are not established Standardized engineering controls, procedures, practices, and personal protective equipment (PPE) Consists of ranges in which exposures to a compound should be controlled; varies by company Typically by laboratory and production operations

7 Performance Based Exposure Control Group OEL Range Design 1 > 1000 g/m 3 General room ventilation. Conventional open equipment with local exhaust ventilation (LEV) 2 50 to 1000 g/m 3 Semi-closed to closed material transfers; laminar flow/directionalized laminar flow, engineered LEV to 50 g/m 3 Transfers using direct coupling & closed systems (SBV), selected use of unidirectionalized air flow booths. 4 1 to 20 g/m 3 Totally enclosed processes; transfers using direct coupling; barrier/isolator technology. 5 < 1 g/m 3 Isolator technology; remote operations, fully automated.

8 Typical Pharmaceutical Containment Program Elements Performance Measurement Industrial Hygiene Workplace Monitoring Direct method for OELs Air and surface sampling Containment Equipment Factory Acceptance Testing surrogate testing in addition to leak tests Site Acceptance Testing

9 Why Contain? Safer processes for employees New drugs are much more potent Patient dosage significantly lower Long term reliance on personal protective equipment Increasing Potency Comparative Dosing & Potency Percent of Compounds Exposure Band Historical New mg Older to newer

10 Why Contain? Good Fit with Quality Minimize potential cross contamination Cleaning enhancements Business/Regulatory/Benchmarking Drivers Regulations emphasize engineering controls Improves process safety Minimize product loss & volume of solid waste Reduce liability Bottom Line - it is good for the industry

11 Containment Philosophy Historical Control Strategy - room as primary containment Isolate surrounding environment in contained rooms Isolate people with personal protective equipment Tremendous initial and operating costs

12 Containment Philosophy Current Control Strategy: contain-at-source Isolate the product in a closed system; provides controlled contained environments Minimizes risk of exposure from potent compounds Minimizes risk of contamination of product from microbiological and particulate Operators work in shirt sleeve environment

13 Hierarchy of Containment Technology Automation/Robotics Isolators/Closed Transfers Directionalized Laminar Flow Laminar Flow Local Exhaust General Exhaust Open Operations

14 Rigid or Hard Wall Isolators

15 Transfer - Alpha Beta Port The use of an Alpha Beta port Allows rapid rotational docking between two devices Contamination on seals