How to Build/Set up a Pharmaceutical Plant

Question by GMP Inspector at Ministry of Health in XXX:

Setting up a pharmaceutical plant - Hi, does anybody knows if there are some publishing or specialized text about Setting up a pharmaceutical plant? thanks in advance

Response by Poster PM:

The scope of the question is very, very large in that:

1) The content of '..set up..' is not specified. This could include (but is not limited to) any or all of the following - design, construction, equipment, services, validation, technical transfer, regulatory approval, documentation, staff training.

2) There is no indication of dose form type - the plant and activities listed under 1 will be dictated by this.

3) There is no indication of the type of API - some including beta lactams, genotoxics, sensitisers, high potency compounds and controlled drugs will require specialised/dedicated facilities and/or licenses.

I do not know of any single publication which would have the necessary scope. If it is possible to identify specific topic areas, there is a lot of guidance available on the internet which would be helpful.

Response by Poster MA:

In my early days, I have also asked similar questions to my supervisor. Is there any book to understand it? As various dosage drug required various good practice so he briefly explain those days how things are done. Please check the following summary:

#Project Approval (Budget, Forecast, Volume, Dosage Form)

#Land selection (very important which dosage form you intend to produce)

#Conceptual Design as per QbD and Regulatory GMP/FDA compliance by related field expert. (Process flow is required by the designer)

#Finalization of Layouts (Area classification, personnel flow, materials, waste flow, emergency evacuation)

#Architecture and civil structure design

#Basic Design (AHU zone, Process equipment, utilities calculation etc)

#Structure design and pilling works

#Detailed design Development fit into the building such as HVAC, PW, Clean room, clean and black utilities etc

# Process equipment finalization (As R&D people, for intended drug manufacturing required process flow)

# Building constructions completion

# Equipment installation and qualifications

# Process validation (If your R&D people developed drugs in lab then just scale up the equipment’s and completes process validation within short time)

# Start production

# Invite regulatory auditors to inspect site to enter various market

Response by Poster MR:

Its a simple question but there is no simple answer. The Pharma industry is highly regulated however regulations do not tell you how to do things only what you must do. So first you define what you want to do (i.e make pills / injectable (parenteral) / vaccines/ medical devices) Then recognise the regulations you need to follow based upon the market you want to sell to. You now need to develop procedures which will satisfy all your regulatory requirements. You may wish to use quality standards such as ISO 9001 or ISO 13485. The data derived provides a record of what was done. Basically you state what you do(regulation). How you do it (Procedure). And prove you did it as required (records). Armed with this information you can apply and get recognition as a pharmaceutical manufacturer.

Response by Poster MD:

You have to decide which dosage forms firstly, secondly the market so you might omit some steps accordingly

Response by Poster CI:

You have some interesting responses, but I noted that you are a health inspector. Therefore, you need the short version. First, I will suggest that you review the publications by ISPE (www.ispe.org). For sterile facilities, there is the PDA (www.pda.org). I believe that you will find these useful. The USFDA provides a roadmap for inspection in their inspection guidelines (www.fda.gov). I will also suggest that if you can afford it, travel to Houston, Texas for the AFDO meeting in June (www.afdo.org). At AFDO, you will meet most of the senior inspection staff at USFDA - Brazil, Mexico, BSI, and Health Canada are attending. If you have any specific questions, I am happy to answer or I know who can. Another great resource is the USP (www.usp.org). You have some great contacts already on this response.

Response by Poster CM:

Invest in the ISPE baseline guides, they could serve as a starting point and as reference guides

Response by Poster MPOA:

Yes, ISPE baseline guides commented previously and also it could be useful:

Guidance for Industry: .-" Q7A Good Manufacturing Practice Guidance for Active Pharmaceuticals Ingredients". .- "Quality Systems Approach to Pharmaceutical CGMP Regulations."

.- ISO 14664-7 (associated a Cleanrooms)

At the end if you need more specific details, you could contact with an Engineering Consultancy in relation to Pharmaceutical Plant design construction.

Response by Costas Chantzis:

Others have posted information about where you could find documentation for the various regulations, etc. I am sure there is plenty of added info/data in the public domain, e.g. or published books but in bits and pieces.

I will outline below how you may want to proceed. I believe you will find the below plant design approach NOWHERE published. It is original. Yet, you can ask the opinion of professional experts in pharmaceutical plant building, commissioning, etc. and I bet they would agree with my proposed approach as being appropriate, sound and valid in principle.

I have been involved in the construction, commissioning and start-up of a new factory in England, one in Mexico, one in Puerto Rico, one in India, two in Japan and numerous such factories/related activities throughout the USA:

1. Site selection:

Must be near an area having a relatively cool temperature: Heat typically significantly accelerates degradation of materials, products and requires increased energy for cooling. Next, it must be near a paved road, closed to a harbour and railroad for transportation of materials, end product. Also, must have access to stable and continuous water, electricity, gas or other energy means but must be away from earthquake prone, water-flood or nuclear power plant or other significant type of calamity. Finally, must be in an area where there would a stable and continuous pool of quality employees at reasonable wages. My preference would be a location at the slope of a mountain to provide added protection from tornadoes, typhoons while having relatively lower temperature.

2. Architectural Site Design:

If we assume the plant will be build at a mountain's slope then it should have two or more floors:

2.1 The 1st floor must house - the various Utilities (water, steam, compressed air) except those of Electricity and Gas, if used, at the space adjacent to the mountain slope; next all Laboratories/ Maintenance Dept, Office space for Personnel; and finally the Finished Product Warehouse at the opposite side of the mountain slope (downhill expansion of warehouse storage can be made later on, as might be required.)

2.2 The 2nd floor or floors above it must house all Incoming Raw Materials at a space adjacent to the mountain's slope and directly above the space where the Incoming Materials are stored on the 1st floor, plus all Manufacturing Processes.

2.3 Separate building that would be properly designed, will house the Electrical Power Grid at the top Left section of the site to prevent/minimize accidental fire or explosion.

2.4 Separate building that would be properly designed, will house the gas utility at the top Right section of the site to prevent/minimize accidental fire or explosion.

2.5 Air Conditioning Utilities will be located near or the top of the site given heat rises.

3. Project Plan

3.1 Build and install/qualify/validate all utilities plus the 1st floor of the plant as described above.

3.2 Build and install/qualify/validate the 2nd floor as described above.

Note:

I suggest you hire at least one or more experts to help you complete this project. Good Luck!