Memorandum

To: Integra LifeSciences

CC: Kalpesh Patel, Brian Vista, Elaine Lu, Ji-Young Lo

From: James Ranlet, Principal Engineer, Hyde Engineering + Consulting, Inc.

Date: 1/31/2018

Re: Recommendations for Cleaning Detergent for Integra

As part of the enhancement of the cleaning processes in Building 105 at Integra

LifeSciences, Hyde Engineering + Consulting, Inc., has performed an evaluation of the
cleaning requirements for the process area.

In the “Integra Residue Study Report”, Keith Bader of Hyde Engineering + Consulting, Inc.,
states that “Sodium Hydroxide was found to be more effective in removing the worst case
residue than both MetriZyme and Sodium Alkyl Sulfate.”1 The study also found that “CIP-
100 has a significantly greater removal rate with regards to the Helistat residue and a
competitive removal rate in comparison to the IAS residue and sodium hydroxide
detergent”1.

The report concludes, “After analysis of the theoretical and empirical cleaning study and the
range finding results from the range finding tests done on Integra’s currently used
detergents, it is recommended that a formulated cleaning agent (such as CIP-100, Dober’s
Chematic 82, or VAI’s Process2Clean1) be used at a high Reynolds number and
temperature in order to improve the removal of worst case residues that may be present and
provide even greater assurance that residues will be removed by maintaining current levels
of external energy input.”1

A study performed by STERIS and others, entitled “Reducing the Risk of Surface Prion
Contamination”, indicates that Steris Corporation detergents HAMO 100 PID and CIP-150
demonstrated the greatest protein removal efficacy when compared to other tested
chemistries.2

In the paper, “Guideline for Disinfection and Sterilization of Prion-Contaminated Medical

Instruments”, William A. Rutala and David J. Weber state that HAMO 100 (not currently
licensed for use in the US, according to Steris) and CIP-100 “could significantly reduce the
infectivity of TSE agents” and list “Alkaline detergent (specific formulations)” and “Chlorine,
> 1000 ppm” at the top of the chart titled “Effective (>3log10 reduction within 1 hour at
temperatures of 20°C-55°C)”3.

Many other studies have shown similar results for alkaline cleaners at > 1.5%
concentrations and temperatures of 35°C to 50°C.

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Depending on the manufacturing process and equipment materials, Integra currently utilizes
Sodium Hydroxide or Sodium Lauryl Sulfate as detergents for cleaning of manufacturing
equipment. The equipment is then separately sanitized with a solution of 6.15% Sodium
Hypochlorite.

Based on Hyde’s study of Integra’s process soils, product-contact materials, and current
cleaning and sanitizing agents, as well as on extensive past experience in the areas of
cleaning and sanitization, Hyde recommends changing from the currently used detergent(s)
to STERIS CIP-150 for all non-aluminum product-contact surfaces. The caustic in CIP-150
is not likely to react to Hard Anodized or Nituff™-coated aluminum due to the high level of
surface protection, but it is recommended that these surfaces be tested in order to confirm
compatibility with caustic detergents prior to cleaning with CIP-150. Non-anodized or non-
coated aluminum should not be cleaned with caustic. Any unprotected aluminum surfaces
that may be in current use would require further study in order to determine the most
effective detergent.

The active ingredients in Steris’ CIP-100, as tested in the Integra Residue Study Report, by
Hyde, are Potassium Hydroxide and Tetrasodium EDTA. The active ingredients in CIP-150
are Potassium Hydroxide, Sodium Hydroxide, and Sodium Hypochlorite. Both detergents
include surfactants and chelating agents. These agents enhance cleaning, soil and mineral
removal, and rinse-ability.

Hyde additionally recommends that the use of a separate Sodium Hypochlorite sanitization
be discontinued, and that Integra qualify the use of STERIS CIP-150 where possible for
both cleaning and sanitization, possibly continuing the use of medical grade Sodium
Hypochlorite for sanitization only where CIP-150 cannot be utilized. In addition to providing
optimized production soil removal through oxidation, the Sodium Hypochlorite in CIP-150
will fulfill the current surface sanitization requirement. Sodium Hydroxide was shown in the
studies listed1,2,3 to have excellent protein removal characteristics and with Sodium
Hypochlorite taking the place of the sanitizing agent currently used, CIP-150 will provide
both sanitization and improved soil removal. When combined, Sodium Hydroxide and
Sodium Hypochlorite have also been shown to have superior TSE protein removal and
deactivation characteristics 2,3.

References:
1
Integra Residue Study Report; K. Bader, Hyde Engineering + Consulting, Boulder, CO.;
Rev. 0.1, 09 Dec 2011; Integra Report # R-2011-176
2
Reducing the Risks of Surface Prion Contamination, G. McDonnell, K. Antloga, M.
Bernardo, H. Kaiser, STERIS Ltd. Basingstoke, UK. G. Fichet, E. Comoy, C. Duval, J.P.
Deslys, CEA/DSV/DRM/GIDTIP, 18 Route du Panorama, 92265 Fontenay-aux-Roses,
France.
3
Guideline for Disinfection and Sterilization of Prion-Contaminated Medical
Instruments, W. Rutala, PhD, MPH and D Weber, MD, MPH; Infection Control and Hospital
Epidemiology, Vol. 31, No. 2 (Feb, 2010), pp. 107-117.

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