Regulatories for Biotechnologies for Life Sciences

“Material, sufficiently homogeneous and stable with respect to one or more specified properties, which has been established to be fit for its intended use in a measurement process”

Four stages:

1st: Definition of context: Legal framework, Protection goals, Project Objectives, Biology of Bacterium, Receiving medium, Track record of safe use

2nd: Formulation of the problem and hazards list

3rd: Risk characterization

4th: Risk estimation (also: Disposal method)

-procedure: SNP analysis

-the process: rt PCR

-parameters: binding affinity for the primer/ probe

- any instrument, appliance, software, or material intended by its manufacturer to be used specifically for diagnostic or therapeutic purposes

- necessary intended to be used for human beings

- does not achieve its intended action by pharmacological, immunological, or metabolic means, but may be assisted in its function by such means.

- "articles" used in combination are also defined as medical devices

A medicinal product is any substance presented as having properties for treating or preventing disease in human beings

Or

any substance which may be used in human beings either with a view to restoring, correcting, or modifying physiological functions by exerting a pharmacological... what !?

In vitro diagnostic medical device is a device which is intended to be used for the examination of specimens derived from the human body. (Device working outside the body)

In vivo diagnostic medical devices can be used in or on the human or animal body (device working inside the body).

conformity assessment means the process demonstrating whether specified requirements relating to a product, process, service, system, person or body have been fulfilled. (e.g. testing, calibraton, inspections, certification)

I: Risk evaluation

II: Risk control

III: Risk communication (documentation)

IV: Risk Review

Start with I again.

1. Quality Management System

2. Risk Management System

3. Technical Documentation

4. EU Declaration of Conformity

5. CE-Marking

6. System of Post-Market Surveillance (PMS)

Basic Elements:
- Quality Management
- Personnel
- Documentation
- Production
- Quality Control
- Complaints and Product Recalls
- Self Inspection/Audit

The CE marking indicates the conformity of the product with health and safety standards.

The CE marking is affixed on products that will be placed on the EEA and Turkish market, whether they are manufactured in the EEA, in Turkey or in another country.

Observance of all aspects of production activites to assure quality

ISO 9001:2015                                                        
> Stand-alone standard
> General requirements for a QM system
> Generically applicable   
> Risk based thinking for planning and realization of processes of the QM system

ISO 13485:2016
> Stand-alone standard, but based on ISO 9001 regarding general QM criteria
> Specific requirements of the QM systems for medical devices sector
> Only applicable in the sector of medical devices
> Application of risk management for the safety and performance of medical devices and with regard to the fulfillment of    regulatory requirements

- Document controls

- Quality policy & manuals

- Standard operating procedures

- Work instructions

- Forms

See picture

1. Good laboratory practice (GLP) for early stages of drug development
2. Pre-clinical studies
3. Good manufacturing practice (GMP) for the manufacturing of clinicla product throughout the drug production
4. Good clinical practice (GCP) for/during the clinical studies/trials

- the procedure: Immunoassay

- the process: measures the presence or concentration of a macromolecule or a small molecule in a solution through the use of an antibody (usually) or an antigen (sometimes).

- the parameters that make protein analysis difficult: binding affinity of the antibody, structure of the protein, function of the protein. In addition the absorbance depends on the type of protein analyzed (different proteins have different amino acid sequences).

Conformity assessment is the process used to show that a product, service, or system meets specified requirements. These requirements are likely to be contained in an ISO standard.

Directive 98/79/EC, Article 1, defines IVDMDs as follows: “in vitro diagnostic medical device”: any medical device which is a reagent, reagent product, calibrator, control material, kit, instrument, apparatus, equipment, or system, whether used alone or in combination, intended by the manufacturer to be used in vitro for the examination of specimens, including blood and tissue donations, derived from the human body, solely or principally for the purpose of providing information:

- concerning a physiological or pathological state,

- concerning a congenital abnormality,

- to determine the safety and compatibility with potential recipients,

- to monitor therapeutic measures.

ISO 13485

4 classes (I, IIa, IIb, III):
I. Lowest risk classification. Non-sterile and/or non-measuring function; No notified Body involvement.
IIa. Manufacturing systems audit
IIb. Manufacturing & product design audit (Technical File)
III. Highest risk classification. Manufacturing & Design Dossier audit   

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)