Quality assurance aspect in the production of PZC based 99mtc generator

QUALITY ASSURANCE ASPECT IN THE PRODUCTION OF PZC BASED 99MTC GENERATOR Le Van So Nuclear Research Institute, Dalat , Vietnam BASIC ELEMENTS OF QUALITY MANAGEMENT • Appropriate infr

FOURTH FNCA COORDINATORS MEETING

March 5 – 7, 2003 , Naha-shi , Okinawa , Japan

FOURTH FNCA COORDINATORS MEETING

- 2003 -

QUALITY ASSURANCE ASPECT IN THE PRODUCTION OF PZC BASED 99MTC

GENERATOR

Le Van So

Nuclear Research Institute, Dalat , Vietnam

BASIC ELEMENTS OF QUALITY MANAGEMENT

• Appropriate infrastructure

i.e., Quality Policy and “Quality System”

– organizational structure

– procedures

– processes

– resources

• Systematic action
QA

• Commitment and Involvement of top executives

QA : is defined as the

sum total of the

arrangements made with

the object of ensuring that

products will be of the

quality required for their

intended use

GMP : is that part of QA

aimed at ensuring that

products are consistently

manufactured to a quality

VALIDATION:

• Prospective Validation :

Which is conducted prior to the commercial distribution of

a new RP or a RP made by a new or revised process

• Concurrent Validation:

Which is conducted for a process in which the RP is being manufactured on a production scale before completion of process

- Prospective

- Concurrent

- Retrospective

Other Quality Aspect

GMP Manufacturing

QC

appropriate to their

intended use

QC : is that part of GMP

which is concerned with

the sampling,

specification and testing ,

and with the organization,

documentation and

release procedures which

ensure that the necessary

and relevant test are, in

fact, carried out and that

materials are not released

for their intended use, nor

products released for sale

or supply, until their

quality has been judged to

be satisfactory

validation studies

• Retrospective Validation :

Which is conducted for a RP already manufactured on a production scale basesd on accumulated production testing and control data

OTHER QUALITY ASPECT:

( Functions&Responsibilities , Non conformances /corrective preventive action analysis …)

ELEMENTS OF GMP

1 Premises and Environment

2 Equipment

3 Personnel

4 Documentation

5 Manufacturing procedures

– Raw materials

– Processing procedures

– In-process testing

– Processing control

– Labelling / packaging / Storage / Shipping

6 Quality control

7 Contract manufacture

8 Import

9 Consignment control

10 Product complaints / Recall

11 Internal audit system

12 Product evaluation and launch protocol

Product evaluation

- Clinical trial

Product launch protocol

Ten Commandments of GMP

– We should write procedures

– We should follow our written procedure

– We should document (record) our work

– We should validate our work

– We should design and build proper facilities and equipment

– We should maintain our facilities and equipment

– We should be competent (as a result of education, training and experience)

– We should be clean

– We should build in quality not test quality in your product

– We should audit for compliance

EVALUATION STUDIES ON THE PROCEDURE OF PZC

1 Outline of the technology for PZC based 99m Tc generator

production

Table 1: Outline of the technologies for 99mTc generator production

Raw materials

(Commercia

l products) and preparation

Hot cell process 1 Hot cell process 2

(Finished generator

assembling –Hot

assembling)

Inactive clean-room process

(Generator components assembling,

Cold Assembling)

Fission

based

generator

-Fission

99

Mo solution -Al 2 O 3

adsorbent

– Dispensing 99Mo stock solution

– Dispensing 99Mo stock solution – 99Mo adsorption

on Alumina column Gel based

Generator

- (n,γ) 99

Mo solution

- Chemicals ZrOCl2,…

– Chemical synthesis and preparation of gel powder – Dispensing gel and column loading

PZC-based

Generator

- (n,γ) 99

Mo solution

- PZC

adsorbent

– Dispensing 99Mo solution and

99

Mo adsorption – Column loading

2 QA & GMP Requirements for a new (PZC based)procedure for 99m Tc generator production

• Raw materials

o Finished 99mTc generator product design and generator component preparation

o PZC adsorbent ( Specification )

7

• Equipment and facilities

o Mo-99 adsorption and PZC column loading machine

o Hot cell facility arrangement – Manipulator and conveyor

• Procedure (standard procedure)

o Description of process

– 99Mo Adsorption

– Loading 99Mo –PZC column

– Generator component cold and hot assembling

o Raw material control

– 99Mo Solution (radioactivity and Molybdenum content)

– PZC and Al2O3 adsorbent (99Mo Adsorption capacity, 99mTc elution yield, Mo and Zr breakthrough , particle size, stability)

– Generator components (column ,solution- line…)

– Elution kit (saline and evaluated vials)

o In-process control

– Radioactivity of solution (pre-and post- adsorption)

– pH of solution (pre- and post- adsorption)

– Temperature and time of adsorption

– Radiation protection monitoring

• Quality Control

o Product specification of Pertechnetate solution eluted from PZC based Tc-99m generator

o Testing procedure (pH, Radiochemical purity, Radionuclide identification,

o Radionuclidic purity, Chemical purity

(Aluminium, Zirconium content , Sterility, Bacterial Endotoxin )

• Product evaluation and launch protocol

o Pre-Clinical studies

– Biological test (bio-distribution studies in test animal)

– Toxicity test

– Pharmacokinetics studies

– Radiation safety

– Environment assessment including waste disposal studies

o Clinical trials

o Product launch protocol

– Registration

– Market approval