Regulatories for Biotechnologies for Life Sciences

Validation, Verification, Compliance, Recall, Quality Control

The Common Technical Document (CTD) is a set of specifications for a dossier for the registration of medicines. The CTD was developed by the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) and adopted by the Therapeutic Goods Administration (TGA) in 2004.

The Common Technical Document is organised into five modules. Module 1 is region specific. Modules 2, 3, 4, and 5 are intended to be common for all regions. Conformance with this guideline should ensure that these four modules are provided in a format acceptable to the regulatory authorities.

Good Laboratory Practice (GLP) for early-stage drug development, the pre-clinical studies, Good Manufacturing Practice (GMP) for the manufacture of medicinal product throughout the medicinal product (drug) production, and Good Clinical Practice during the clinical trials. 

= DIRECTIVE (GMP/GLP/GCP)

REG = REGULATION (GMP/GCP)

= international conference on harmonisation of technical requirements for registration of pharmaceuticals for human use (GMP/GLP/GCP/CTD)

= The Organisation for Economic Cooperation and Development (GLP)

Directive 98/79/EC for In Vitro diagnostic medical devices, will become the Regulation 2017/746 for In Vitro diagnostic medical devices. The directive 93/42/EC for medical devices and the directive 90/385/EEC for active implantable medical devices will become the regulation 2017/745 for medical devices.

Corrective and Preventive Action (CAPA) is a Quality Management System (QMS) process

Biosafety is the prevention of large-scale loss of biological integrity, focusing on ecology, and human health. These prevention mechanisms include conduction of regular reviews of the biosafety in laboratory settings, as well as strict guidelines to follow. Biosafety is used to protect from harmful incidents. Many laboratories handling biohazards employ an ongoing risk management assessment and enforcement process for biosafety.

Biosecurity refers to measures aimed at preventing the introduction and/or spread of harmful organisms (e.g. viruses, bacteria, etc.) to animals and plants in order to minimize the risk of transmission of infectious disease.

First stage: Definition of context: Legal framework, Protection goals, Project Objectives, Biology of Bacterium, Receiving medium, Track record of safe use

Second stage: Formulation of the problem and hazards list

Third stage: Risk characterization

Fourth stage: Risk estimation (also: Disposal method)

Pro-Tip: Work with a bacterial strain of lower biosafety level.

Risk group 2: E. coli Wildtyp

E.g. E. coli K-12: common laboratory strain e.g. used for cloning experiments.
No pathogenic factors.
Risk assessment: S1 (same for E. coli XL-1 blue)

What he said: planning to work with a bacterial strain within the lowest biosafety level.
E.g. E. coli Wildtyp to E. coli XL-1 blue or E. coli K-12.

ISO 13485

A notified body, in the European Union, is an organization that has been designated by a member state to assess the conformity of certain products, before being placed on the EU market, with the applicable essential technical requirements. These essential requirements are published in European directives or regulations.
More generally, a notified body is an independent, accredited body that is entitled to an authorized accrediting body. Upon definition of standards and regulations, the accrediting body may allow a notified body to provide verification and certification services. These services are meant to ensure and assess compliance to the previously defined standards and regulations, but also to provide an official certification mark or a declaration of conformity

Technical: 
Annual check of the filters 
Label, Benches with class 2 
Autoclave with spore tests.  

Administrative: 
labeling of the working area
access only for authorized lab members
operation instructions
arrangements for accidents
regular biosafety lectures for the lab members
documentation of all the lab work
Hygiene plan

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Risk assessment meets biotechnology (ISO 14971)

• Risk Assessment
– Overall process comprising a risk analysis and a risk evaluation
• Risk Analysis
– Systematic use of available information to identify hazards and to estimate the
risk
• Risk Evaluation
– Process of comparing the estimated risk against given risk criteria to determine
the acceptability of the risk
 

-> tool for risk minimization: using natural non-pathogenic MO!?

S1 Biological material, which is non-pathogenic, and consequently unlikely to cause human diseases.
eg. E.coli K-12

S2 Biological material, which can cause human diseases, and
consequently is dangerous for the employees.
Risk of spreading: unlikely
Prophylaxis and therapy: possible
eg. Influenza A Virus

S3 Biological material, which can cause severe human diseases,
and consequently is seriously dangerous for employees.
Risk of spreading : latent
Prophylaxis and therapy : possible
eg. Mycobacterium tuberculosis

S4 Biological material, which can cause severe human diseases, and consequently is seriously dangerous for employees.
Risk of spreading : high
Prophylaxis and therapy : NOT possible
eg. Ebola Virus

 

Medical devices are in vitro diagnostic medical devices (IVDs) if they are reagent, calibrator, control material, kit, specimen receptacle, software, instrument, apparatus, equipment, or system, whether used alone or in conjunction with other diagnostic methods.

A notified body, in the European Union, is an organisation that has been designated by a member state to assess the conformity of certain products, before being placed on the EU market, with the applicable essential technical requirements. These essential requirements are publicized in European directives or regulations.

A manufacturer can use voluntarily European harmonised standards to demonstrate that a product complies with some (or all) of the EU essential requirements; a notified body can use the same harmonised standards to assess the conformity to these essential requirements. Conformity assessment can include inspection and examination of a product, its design, and the manufacturing environment and processes associated with it. For example, a notified body may designate that a medical device conforms to the Medical Devices Regulation (MDR (EU) 2017/745) which defines the applicable legislation, including the general safety and performance requirements, for medical devices. With this declaration of conformity, the manufacturer can label the product with the CE Mark, which is required for distribution and sale in the EU. Additionally, the EU member state accrediting the notified body will then inform the European Commission that the product complies with set standards (or not).

risks are divided depending on their likelihood & their effects or the extent of damage

-> worst-case scenario can be determined at a glance
-> result of the risk analysis and risk evaluation
     ->important component of project & risk management

A risk matrix is a matrix that is used during risk assessment to define the level of risk by considering the category of probability or likelihood against the category of consequence severity. This is a simple mechanism to increase the visibility of risks and assist management decision making.

Evaluating the risk:
Likelhood
1. Highly unlikely
2. Possibly
3. Quite likely
4. Very likely

Severity
1. Slight harm
2. Injury affecting work
3. Serious injury
4. Possible fatality

╭ᑎ╮ DIC ╭ᑎ╮
• Decide measures to be taken
• Implement them according to priority
• Confirm measures appropriate and work