Passivation of stainless steel is a process that cleans the steel's surface with acid to remove free iron and create a chromium-rich surface, improving chemical resistance. It is important for pharmaceutical equipment as some common manufacturing substances can corrode 316L alloy. Regulations in North America require that equipment surfaces not react with, add to, or absorb drug components in a way that alters safety, identity, strength, quality or purity.

2. Definition
Why is important?
Regulation in North America

3. Passivation of stainless steel is to clean its surface with
an acid for the purpose to remove free iron and create a
chromium rich surface.
FeFe FeFeFe
FeFe FeFe
Cr Cr
CrCrCr

4. Interior of a tank used to prepare large
volume parenterals
Pump casing after 1 year in service
pumping pure water
Inside of a clean steam system

5. Some substances common in the drug manufacturing
process are corrosive even to the 316L alloy.
Those substances are:
• High purity water (purified water, WFI etc.)
• Pure steam
• Saline solutions
• Chlorine compounds (Benzalkonium chloride, hydrochloric
acid, etc.)
To improve the chemical resistance of stainless steel this one
must be passivated.
It is a common industrial practice that all stainless steel
surfaces in contact with raw materials or finish product should
be passivated to prevent any potential reaction with the alloy

6. In the 300 series stainless steel the chromium oxide
in the passive layer is created spontaneously with
the air, but its composition is enhanced by some
acids such as nitric or citric.
The 316 alloy is more corrosion resistant than 304.
The L grade will improve the properties of welds.

7. The most common stainless steel alloys used to
manufacture pharmaceutical equipment in North America
are types 316L, 316, 304 and 304L as per American Iron
and Steel Institute.
However above alloys are mostly iron.
316L 316 304L 304
Iron 62.1-69.1 62.0 -69.1 66.6 -71.1 64.2-71.1
Chromium 16.0-18.0 18.0 - 20.0
Nickel 10.0-14.0 8.0-10.5 8.0-12.0
Molybdenum 2.00-3.00 ---------
Manganese Max 2.00
Silicon Max. 0.75
Phosphorus Max. 0.045
Sulfur Max. 0.030
Carbon Max. 0.030 0.080 0.030 0.080

8. In the 300 series stainless steel, the corrosion resistance is given by a
molecular layer called passive layer.
The passive layer does not have the same composition as the bulk alloy. It
has mostly iron and chromium in the form of chromium oxide.

9. If the passive layer has more
iron, is more prone to corrosion
Fe Fe FeFeFe FeFe CrOX CrOX

10. If the passive layer has more
chrome, is more corrosion resistant
FeFeFe Fe FeCrOXCrOXCrOXCrOX

11. “Equipment shall be constructed so that surfaces
that contact components, in-process materials, or
drug products shall not be reactive, additive, or
absorptive so as to alter the safety, identity,
strength, quality, or purity of the drug product
beyond the official or other established
requirements.”
Regulation
21CFR211.65(a)
shall not be reactive,

12. “No person shall sell any drug that
(a) Was manufactured, prepared, preserved
packaged, or stored under unsanitary conditions”
Regulation
In Canada the Food and Drugs Act requires:
No
unsanitary conditions

13. “C.02.005
The equipment with which a lot or batch of a drug is
fabricated, packaged/labelled or tested shall be designed,
constructed, maintained, operated, and arranged in a
manner that
(b) prevents the contamination of the drug and the
addition of extraneous material to the drug;”
Regulation
Canadian Good Manufacturing Practices (GMP)
Guidelines - 2009 Edition, Version 2 (GUI-0001)
equipment
prevents the contamination

14. Mauricio Gonzalez has more than 7
years of experience executing
passivation, pickling and sanitization
projects in the pharmaceutical
industry.
My experience include trouble
shooting high purity generation and
distribution systems when
passivation, derouging or sanitzation
may be required.
MauricioG.Career@gmail.com
Voice:Luis Gonzalez